X CONGRÉS...described (Franco-Jarava et al. J Clin Immunol 2016; 36:388-96) that standard capillary protein electrophoresis can be used to detect sera which may have low C3 levels

X CONGRÉS

Societat Catalana d’Immunologia (SCI)

Programa Final

Barcelona, 17 i 18 de Novembre de 2016

Immune response: T-cells attack a cancer cell. CREDIT: MAURIZIO DE ANGELIS / SCIENCE PHOTO LIBRARY / GETTY IMAGES

Immunoteràpia contra el Càncer

Cancer Immunotherapy

2 www.sci.cat

Organization Committee (SCI Board): Welcome to the Congress,

On behalf of the organising committee, we would like to warmly welcome you to the

Xth Societat Catalana d’Immunologia (SCI) Congress. We believe that our meeting will

present high level scientific knowledge with the contribution of immunologists and

specialists who are experts in this field.

Dr. Cándido Juárez

SCI President

Xth Congress of the Catalan Society of Immunology: Immunotherapy against cancer, has been accredited by the Catalan Lifelong Learning Board of the Healthcare Professions with 0.8 credit (Expedient: 09/017183-MD, 29-08-2016)

President: Dr. Cándido Juárez Secretary: Dr. Francesc Rudilla Treasurer: Dra. María José Amengual Vice President: Dra. Annabel Valledor Member: Dra. Mónica Martínez Gallo Member: Dr. Jordi Bas Member: Dr. Carles Morte Member: Dra. Irene Puga

Congress Office: Sr.Xavier Nieves ([email protected])

www.sci.cat 3

This Congress is sponsored by:

Gold Sponsor

Silver Sponsors

4 www.sci.cat

Content

Immunoteràpia contra el Càncer .......................................................................................... 1

Cancer Immunotherapy ....................................................................................................... 1

This Congress is sponsored by: ........................................................................................... 3

Content ................................................................................................................................ 4

Scheme first day .................................................................................................................. 5

Scheme second day ............................................................................................................ 6

Corporative Abbreviations .................................................................................................... 8

Abstracts .............................................................................................................................. 9

Oral Communications Session I Clinical Immunology 1 - 5......................................... 9

Oral Communications Session II Immune Response 6 - 10...................................... 14

Oral Communications Session III From Innate to Adaptative Immunity 11 - 15 ........ 19

e-poster List ....................................................................................................................... 24

Posters Clinical Immunology 1 - 4 .................................................................................. 24

Posters Diagnostic Immunology 5 - 9 ............................................................................. 28

Posters Immune Response 10 - 15 ................................................................................ 33

Posters Innate Immunity 16 - 19 .................................................................................... 39

2017 Events ....................................................................................................................... 43

Lifelong Learning SCI Program 2017 ............................................................................. 43

New members .................................................................................................................... 44

Registration form to SCI ................................................................................................. 44

Participant information ....................................................................................................... 44

Useful information .......................................................................................................... 45

List of participants and authors ...................................................................................... 46

Other useful information and notes ................................................................................ 48

Awards to the best communication and to the best poster at the X Congress SCI 2016, sponsored by SCI

This year SCI sponsors the awards for the best communication (400 €) and for the best poster (250 €) of this congress. The Chairpersons of the different sessions of the congress and the board members of the SCI will select the best oral communications presented, taking into account its scientific values and the aspects related to the presentation. The poster awarded will be chosen by the congress attendees activating the electronic vote inside the electronic panels of the posters. The results will be announced at the end of the congress.

www.sci.cat 5

Scheme first day

Thursday, November 17th

15:30 17:30

Arrival, Registration and Documentation delivery

16:20 16:30

Welcome to the Xth CONGRESS of SCI Dr. Cándido Juárez (President of SCI)

16:30 17:30

Chair: Dra. Annabel Valledor (UB)

Dr. MARTIN PULE University College London Hospitals (United Kingdom)

“CARs in the Future”

17:30 17:45

Poster viewing – Coffee Break Posters can be viewed on the 4 electronic panels located in the Hall

17:45 18:45

Chair: Dr. Oscar de la Calle (HSCSP)

Dr. RAFAEL SIRERA Universitat Politècnica de Valencia (España)

“Microambient and the control of the anti-tumoral response: anti-inhibitors and anti-tumoral modulators. The importance of biomarkers”

18:45 19:45

Oral Communications Session I: Clinical Immunology

Chairs: Dr. Oscar de la Calle (HSCSP) and Dra. Virgina Mas (HUBell) 18.45h How clinical laboratory standard capillary protein electrophoresis alerted to a low C3

state. Clara Franco Jarava et al. (oral presentaton 1).

18.57h ICF syndrome due to a homozygous mutation in DNMT3B gene in two patients with

profound hypogammaglobulinemia but without clear facial dysmorphism. Clara Franco Jarava et al. (oral presentation 2).

19.09h HALIP: A distinct new IFL pattern can increase the rate of HMGCR antibody detection in

statin-associated autoimmune myopathy. Ana Marín Sánchez et al. (oral presentation 3). 19.21h Diagnostic utility of ENAs detection in broncoalveolar lavage of patients at onset of

diffuse interstitial lung disease. Iñaki Salvador Corres et al. (oral presentation 4). 19.33h Adaptive NKG2C

+ NK cells and the risk of cytomegalovirus infection in kidney transplant

recipients. Dolores Redondo-Pachón et al. (oral presentation 5).

19:50 End of session

6 www.sci.cat

Scheme second day

Friday, November 18th

08:30 08:55

Arrival, Registration and Documentation delivery

09:00 10:00

Chair: Dr. Francisco José Pérez-Cano (UB)

Dr. JO VAN GINDERACHTER Vrije Universiteit, Brussels (Belgium).

“New concepts from tumour-associated macrophages”

10:00 11:00

Oral Communications Session II: Immune Response

Chair: Dr. Cándido Juárez (HSCSP) and Dra. Annabel Valledor (UB)

10:00h Isolated De Novo Antiendothelial Cell Antibodies and Kidney Transplant Rejection. Elena Sánchez-Zapardiel et al. (oral presentation 6).

10:12h Olive oil-in-water emulsified mycobacteria trigger a robust immune response both in

vitro and in bladder tumor-bearing mice. Estela Noguera-Ortega et al. (oral presentation

7).

10:24h Oligosaccharides activity in acute gastroenteritis of RV-infected suckling rats. Azagra-

Boronat I. et al. (oral presentation 8).

10:36h Regulatory properties of Statins and Rho GTPases prenylation inhibitiors to stimulate

melanoma immunogenicity and promote anti-melanoma immune response. Guillaume

Sarrabayrouse et al. (oral presentation 9).

10:48h Immune responses in a murine device-related infection model: role of IL-17A. Marina

Sabaté Brescó et al. (oral presentation 10).

11:00 11:30


11:30 12:30

Chair: Dr. Francesc Rudilla (BST)

Dra. ALENA GROS National Cancer Institute Bethesda (USA),

“Anti-tumoral T cells. What can TILs provide in anti-tumoral immunotherapy?”

12:30 13:30

Assemblea General Ordinària SOCIETAT CATALANA d’IMMUNOLOGIA (SCI) (12.30h – First Call) Us hi esperem a tots: els socis i no-socis!!

www.sci.cat 7

13:30 15:00

Poster viewing – LUNCH Posters can be viewed on the 4 electronic panels located in the Hall

15:00 16:00

Chair: Dra. Elisabeth Calderón (Instituto Grifols S.A. Research and Development Area)

Dr. FRANCISCO BORREGO BioCruces Health Research Institute, Barakaldo,

Pais Vasco

“NK cell based cancer immunotherapy”

16:00 16:55

Oral Communications Session III: From Innate to Adaptative Immunity

Chair: Dr. Ramón Gimeno (IMIM) and Dra. M. José Amengual (CSPT)

16:00h Human tolerogenic dendritic cells upregulate EP2/EP3 receptors to potentiate the

immunosupressive activity of PGE2. Georgina Flórez-Grau et al. (oral presentation 11).

16:12h Diving into apoptosis: liposome-based platform for autoimmune diseases. Silvia

Rodriguez-Fernandez et al. (oral presentation 12).

16:24h The mitochondrial protein Mfn2 controls ROS production and inflammation. Juan Tur et

al. (oral presentation 13).

16:36h The phenotipe of B lymphocytes is determinant for autoreactive T cell activation in Type

1 Diabetes. Leire Egia-Mendikute et al. (oral presentation 14).

16:48h Characterization of the pulmonary and systemic immune response in patients with

Chronic Obstructive Pulmonary Disease. Tamara Cruz et al. (oral presentation 15).

16:55 17:20


17:20 18:15

Chair: Dr. Ramón Gimeno (IMIM)

Dr. DANIEL BENÍTEZ IDIBAPS, Hospital Clínic, Barcelona

“Cell adoptive cancer immunotherapy”

18:15 18:30

Prize to the best communication and poster in the Congress, sponsored by SCI, Dr. Cándido Juárez (President of SCI). End of Congress

8 www.sci.cat

Corporative Abbreviations

BST: Banc de Sang i Teixits

CEMCAT: Centre d’Esclerosi Múltiple de Catalunya

CIBER: Centro de Investigación Biomédica en Red

CIBERehd: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y

Digestivas

CRC: Centre de Recherche des Cordeliers

CSPT: Corporació Sanitaria Parc Taulí

HIVACAT: Institut de Recerca de la Sida IrsiCaixa i el Servei de Malalties Infeccioses i

Sida de l’Hospital Clínic de Barcelona

HUGTiP: Hospital Universitari Germans Trias i Pujol

HSCSP: Hospital de la Santa Creu i Sant Pau

HUBell: Hospital Universitari de Bellvitge

HUVH: Hospital Universitari Vall d’Hebron

IBEC: Institut de Bioenginyeria de Catalunya

ICFO: Institut de Ciències Fotòniques

IDIBAPS: Institut d'Investigacions Biomèdiques August Pi i Sunyer

IIB: Institut dÍnvestigacions Biomèdiques Sant Pau

IGTP: Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol

IMIM: Institut Hospital del Mar d'Investigacions Mèdiques

INSA: Institut de Recerca en Nutrició i Seguretat Alimentària

IRB Barcelona: Institut de Recerca Biomèdica Barcelona

IRB Lleida: Institut de Recerca Biomèdica Lleida

PCB: Parc Científic de Barcelona

PRBB : Parc de Recerca Biomèdica de Barcelona

SCI: Societat Catalana d’Immunologia

UAB: Universitat Autònoma de Barcelona

UB: Universitat de Barcelona

UPF: Universitat Pompeu Fabra

VHIR: Vall d’Hebron Institut de Recerca

www.sci.cat 9

Abstracts

Oral Communications Session I Clinical Immunology 1 - 5

1 How clinical laboratory standard capillary protein

electrophoresis alerted to a low C3 state

Clara Franco Jarava1,4

; Roger Colobran Oriol1,3,4

; Andrea Martín Nalda4,5

; Jaume Mestre Torres2;

Guadalupe Gala Yerga1; Esther García Guantes

1; Susana Martos Gutierrez

1; Ricardo Pujol Borrell

1,4;

Pere Soler Palacín4,5

; Manuel Hernández González1,4

1Servei d'Immunologia (HUVH);

2Servei de Medicina Interna. (HUVH);

3Departament de Biologia Cel·lular,

Fisiologia i Immunologia. UAB; 4Vall d'Hebron Institut de Recerca (VHIR);

5Unitat d'infeccioses i

immunodeficiències. Servei de Pediatria (HUVH).

Introduction: Low C3 either secondary to comsumption/low production, to C3 nephritic

factor and antifactor H auto-antibodies or, more rarely, due to deficiencies in the regulatory

proteins factor H, factor I or Factor B or C3 itself, predisposes to infection by encapsulated

microorganisms, and is associated to autoimmunity. In previous studies, we have

described (Franco-Jarava et al. J Clin Immunol 2016; 36:388-96) that standard capillary

protein electrophoresis can be used to detect sera which may have low C3 levels

confirmed by specific assays. We report here the results from the initial 18 months during

which the beta fraction of the proteinograms was systematically checked in our clinical

laboratory.

Materials, methods and results: The beta 2 fraction in 67,753 proteinograms (Capillarys

2, Sebia) wasassesed by a trained technicien. C3 and C4 was measured in all patients

with a flat beta2-fraction (always using a serum obtained less than 8h prior to the test).

When C3 < 50 mg/dL and C4 was normal, the clinical record was analyzed for episodes

infections by encapsulated bacterial. In all the pediatric cases a complete complement

function work-up was carried out. Adults were referred to the Immunology out-patient

Clinic. The analysis was completed with molecular studies when it was appropriated.

Three patients with confirmed low C3 were identified. Two carried an homozygous

mutation in the Factor I gene, and one patient was positive for C3 nephritic factor.

Conclusion: When fresh serum is used, capillary protein electrophoresis can alert of a

state of low C3. This study suggests that factor I deficiency is not as exceptional as

presently presumed (only 40 cases reported). More importantly, patients diagnosed of low

C3 benefit from preventive treatment and genetic counseling.

10 www.sci.cat


2 ICF syndrome due to a homozygous mutation in DNMT3B gene

in two patients with profound hypogammaglobulinemia but

without clear facial dysmorphism

Clara Franco Jarava1,3,4

; Marina Garcia Prat2,4

; Andrea Martín-Nalda2,3,4

; Lourdes García Rodríguez5;

Rosario Díez Martín5; Alberto Plaja

6; Carmen Mediano Vizuete

6; Manuel Hernández González

1,3,4; Pere

Soler Palacín2,3,4

; Roger Colobran Oriol1,3,4

1Servei d’Immunologia. Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Institut de Recerca

(VHIR); 2Unitat de Patologia Infecciosa i Immunodeficiències Pediàtriques. HUVH;

3Universitat Autònoma de

Barcelona (UAB); 4Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies,

Barcelona; 5Servei de Pediatria, Hospital de Mataró, Consorci Sanitari de Mataró;

6Àrea de Genètica Clínica

i Molecular HUVH, VHIR.

Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a

rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin

deficiency, and branching of chromosomes 1, 9, and 16 after phytohemagglutinin (PHA)

stimulation of lymphocytes. The two main entities of this syndrome are ICF1 (#242860)

and ICF2 (#614069), caused by mutations in DNMT3B and ZBTB24 genes respectively.

ICF was first described in 1978, and since then less than 70 ICF cases have been

described worldwide. The prevalence is <1/1,000,000. In this study we described a 4 year-

old patient from a consanguineous family from Gambia. The patient was referred to our

hospital due to growth delay, recurrent pulmonary infections, several episodes of sepsis

(Haemophilus influenza, Pseudomonas aeruginosa, Streptococcus pneumoniae) and

hypogammaglobulinemia. Innate, granulocyte and complement defects were ruled out,

and it was last classified as an antibody defect immunodeficiency. At the age of 7, his

sister was born prematurely with intra- and extrauterine growth delay. The karyotype

displayed in the patient suggests ICF. Both the sister and the patient present no memory B

cells. Despite the absence of characteristic facial features in the patient, the karyotype was

also performed showing signs of chromosomal instability. Genetic studies in both the

patient and his sister revealed a homozygous mutation in DNMT3B gene consisting in a

nucleotide change in exon 16 (c.1747G>A) leading to an amino acid change

(p.Gly583Ser) predicted as pathogenic. Interestingly, this mutation was recently found by

other group in two patients also from Gambia, suggesting the possibility of a “founder

effect” of this mutation in this region. In this study we described two new cases of ICF

revealing that facial dysmorphism is not always present in these patients and consequently

the disease might be underdiagnosed.

www.sci.cat 11


3 HALIP: A distinct new IFL pattern can increase the rate of

HMGCR antibody detection in statin-associated autoimmune

myopathy

Ana Marín Sánchez1; Alvarado-Cardena, M.

3; Martínez, M.A.

4; Martínez-Martínez, L.

4; Pinal-Fernandez,

I.3; Labrador-Horrillo M.

3; Balada E.

3,5; Mundet-Tuduri X.

6; Gonzalez-Mera L.

7; Casademont J.

8;

Martínez-Acebes E.9; Moreno P.J.

10; Juárez C.

2,3; Grau-Junyet J.M.

10; Pujol-Borrell R.

1,2,5; Selva

O'Callaghan, A.3,8

1Servei Immunologia, Hospital Universitari Vall d'Hebron (HUVH);

2Departament de Biologia Cel·lular,

Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB); 3Internal Medicine Department, HUVH,;

4Immunology Department, Hospital de la Santa Creu i Sant Pau (HSCSP), IIB Sant Pau,;

5Vall d'Hebron

Institut de Recerca (VHIR); 6Unitat de Suport a la Recerca Barcelona ciutat, IDIAP Jordi Gol;

7Neurology

Division, Hospital de Viladecans; 8Internal Medicine Division, HSCSP;

9Neurology Division, Hospital Infanta

Leonor, Madrid; 10

Muscle Research Group, Internal Medicine Division, Hospital Clinic, Universitat de

Barcelona (UB); 11

Department of Medicina, UAB. AMS and MAC contributed equally to this work.

Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has

recently been described. Several specific immunoassays are in use to detect HMGCR

antibodies. In the course of systematic autoantibody screening a new distinct IFL staining

pattern was identified on rat liver sections. This pattern regularly coincided with anti-

HMGCR antibodies. In this study we investigated whether this new IFL pattern is

specifically associated to statin-associated autoimmune myopathy and corresponds to

anti-HMGCR antibodies. Twenty-three patients positive for anti-HMGCR antibodies (14

diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays

and confirmed by immunoblot. HMGCR associated liver IFL pattern (HALIP) i.e., distinct

scattered hepatocytes with centrilobular distribution and a cytoplasmic pattern was

detected by indirect IFL and the reactivity against HMGCR was confirmed by

immunoabsorption using purified human HMGCR antigen. Patients with other autoimmune

diseases (n=90) and non-autoimmune statin treated patients (n=45) were studied as

controls. HALIP was detected positive in 21 out of 23 (91%) HMGCR positive patients.

Statistical concordance between HALIP and anti-HMGCR antibody tests was 98.7%,

kappa 0.95. None of the control sera from autoimmune patients or non-autoimmune statin

treated subjects was positive for HALIP. The HALIP staining was completely and

specifically removed by immunoabsorption with human purified HMGCR HALIP is a new

and distinct IFL staining pattern associated to HMGCR myopathy. Absorption and

concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR

or a closely related protein. Awareness of this new pattern can help to detect HMGCR

autoantibodies in statin treated patients tested for autoimmune serology in which the

associated myopathy is not suspected.

12 www.sci.cat


4 Diagnostic utility of ENAs detection in broncoalveolar lavage

of patients at onset of diffuse interstitial lung disease

Iñaki Salvador Corres1; Alejandro Olivé

2; Carmen Centeno

3; Aina Teniente Serra

1; Bibiana Quirant

Sánchez1; Alex Soriano Martínez

1; Amanda Rus Merchan

1; Eva M. Martinez Cáceres

1; Karina Portillo

3

1Immunology Department, Hospital Germans Trias i Pujol (HUGTiP);

2Rheumatology Department, (HUGTiP);

3Pneumology Department, (HUGTiP).

Introduction: Lung´s interstitium damage is a common manifestation in connect tissue

diseases (CTD), especially in systemic sclerosis and myositis but also in Sjögren

syndrome, systemic lupus erythematosus and rheumatoid arthritis. Having a huge surface

of contact with the exterior media and a resident population of antigen presenting cells,

lung epithelium is a firm candidate for the initialization of autoimmunity after homeostasis

breakdown produced by acute or chronic inflammation. The presence of different

extractable nucleic antigens (ENAs) in serum of patients with CTD has been associated

with a higher risk of developing interstitial lung disease. But the underlying mechanism has

not been defined yet.

Material and Methods: IgG and IgA autoantibodies against ENAs specificities were

studied in 35 samples of bronchoalveolar lavage (BAL) of patients with debut of interstitial

lung disease by immunoblot (Euroimmun). Positive samples were confirmed by indirect

immunofluorescence on Hep-2 cells (INOVA).

Results: Seven BAL samples (20%) were positive for at least one of the studied

specificities (Ro52 (n=5), Jo-1 (n=2), CENP-B (n=2), Ro-60 (n=1) and La (n=1). From 11

patients diagnosed of interstitial lung disease associated with CTD, 6 (55%) had positivity

for at least one specificity. Interestingly, in three of them, the first manifestation of CTD

was interstitial involvement. One patient positive for CENP-B autoantibodies had a positive

nonspecific interstitial pneumonitis (NISP). The Jo-1 positivity was confirmed by IFI

showing a dotted cytoplasmic pattern. The analysis of IgA specificities of ENA provided no

additional data, showing positivity for the same specificities detected with IgG conjugate

but with lower intensity.

Conclusions: Analysis of ENAs in BAL samples can be a useful tool for the diagnosis of

interstitial lung disease, in particular, in those cases associated to connective tissue

disease.

www.sci.cat 13


5 Adaptive NKG2C+ NK cells and the risk of cytomegalovirus

infection in kidney transplant recipients

Dolores Redondo-Pachón*1

; Marta Crespo*1,2

; Jose Yélamos2,3

; Aura Muntasell2; María José Pérez-

Sáez1,2

; Silvia Pérez-Fernández2; Joan Vila

2; Carlos Vilches

5; Julio Pascual

+1,2; Miguel López-

Botet+2,3,4

1Department of Nephrology, Hospital del Mar, Barcelona;

2Hospital del Mar Medical Research Institute

(IMIM), Barcelona; 3Department of Immunology, Hospital del Mar;

4University Pompeu Fabra (UPF),

Barcelona; 5Immunogenetics-HLA, Instituto de Investigación Sanitaria Puerta de Hierro, Majadahonda,

Spain. (authors: *equal contribution,+ shared credit)

Cytomegalovirus (CMV) infection in kidney transplant recipients (KTR) has been

associated with an increased risk of graft loss and reduced host survival. CMV promotes

persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C

(KLRC2) gene is frequently deleted and copy number influences the adaptive response of

NKG2C+ NK cells. The distribution of NKG2C+ NK cells and NKG2C genotypes

(NKG2C+/+, NKG2C+/del, NKG2Cdel/del) was studied in cross-sectional (N=253) and

prospective (N=122) KTR cohorts. Assessment of CMV viremia was restricted to

symptomatic cases in the retrospective study, but regularly monitored in the prospective

cohort. In the cross-sectional study, the proportions of NKG2C+ NK cells were significantly

higher in KTR who had suffered post-transplant symptomatic CMV infection. Yet, in the

prospective follow up (3, 6, 12 and 24 months), post-transplant NKG2C+ NK cell

expansions were not systematically associated with viremia, being detected in some cases

at late time-points. Remarkably, the incidence of post-transplant viremia was significantly

reduced among cases with higher pretransplant levels of NKG2C+ NK cells. The NKG2C

genotypes distribution was comparable in KTR and healthy controls, yet a trend showing

increased NKG2C+/del and reduced NKG2C+/+ frequencies in symptomatic infection was

appreciated in both cohorts. Altogether, our results indirectly support that the dynamics of

post-transplant adaptive NKG2C+ NK cell expansions depends on the degree of individual

control of CMV infection and, more importantly, that these cells may play an active role in

antiviral defense.

14 www.sci.cat

Oral Communications Session II Immune Response 6 - 10

6 Isolated De Novo Antiendothelial Cell Antibodies and Kidney

Transplant Rejection

Elena Sánchez-Zapardiel1; Esther Mancebo

2; María Díaz-Ordóñez

3; Lucía de Jorge-Huerta

3; Lara Ruiz-

Martínez3; Antonio Serrano

2; María J. Castro-Panete

2; Alberto Utrero-Rico

4; Amado de Andrés

2; José

M. Morales2; Sara Domínguez-Rodríguez

3; Estela Paz-Artal

2

1Hospital Universitario Vall d'Hebron;

2Hospital Universitario 12 de Octubre;

3Universidad Complutense de

Madrid; 4Instituto de Investigación Sanitaria I+12, Madrid.

Studies analyzing the role of anti-endothelial cells antibodies (AECA) in large series of

patients are scarce, and HLA, MICA and AT1R have not been formally excluded as

targets. From a cohort of 727 recipients, 324 were negative for HLA, MICA and AT1R

antibodies. Among these, we proceeded to evaluate the presence AECA by indirect

immunofluorescence (IIF) on human vein endothelial cells (HUVEC). Of the 324 studied

patients, 66 were AECA-positive. Within this group, 59% had preformed AECA (Pre-

transplant positive / Post-transplant positive) and 41% had de novo AECA (Pre-transplant

negative / Post-transplant positive). Significantly higher rejection was observed in de novo

vs. preformed or AECA-negative patients (p<0.001). De novo AECA emerged as an

independent risk factor for allograft rejection (OR 5.17, p<0.001). We recorded six different

immunofluorescence patterns on HUVEC and observed that within de novo AECA

patients, only anti-cytoskeleton or anti-nuclear AECA patterns were detected and

appeared in all rejectors (p=0.003). Delayed graft function (DGF) and creatinine at week 1

were significantly higher in de novo vs. preformed AECA patients (p=0.044 and p=0.034,

respectively). Rejection in de novo AECA group was not predominantly humoral or C4d+.

In summary we found that de novo AECA with targets different from traditional alloantigens

relate to rejection. We propose that previous rejections damaged the endothelium and the

dying cells exposed nuclear and cytoskeleton antigens, which elicited the observed

rejection-related de novo AECA. These antibodies might serve as biomarkers of

endothelium damage in renal recipients.

www.sci.cat 15


7 Olive oil-in-water emulsified mycobacteria trigger a robust

immune response both in vitro and in bladder tumor-bearing

mice

Estela Noguera-Ortega1; Núria Blanco-Cabra

1; Rosa Maria Rabanal

2; Alejandro Sánchez-Chardi

3;

Mónica Roldán3; Sandra Guallar-Garrido

1; Eduard Torrents

4; Marina Luquin

1; Esther Julián

1

1Departament de Genètica i de Microbiologia, Facultat de Biociències, UAB;

2Unitat de Patologia Murina i

Comparada, Departament de Medicina i Cirurgia Animals, UAB; 3Servei de Microscopia, UAB;

4Bacterial

Infections and Antimicrobial Therapy group, IBEC.

Mycobacteria are the only bacteria currently used as immunotherapeutic agent for cancer

treatment. Specifically, intravesical administration of Mycobacterium bovis BCG in bladder

cancer patients prevents recurrence and progression of the disease. Recently, the efficacy

of Mycobacterium brumae, a non-pathogenic mycobacteria has also been demonstrated in

in vitro and in vivo studies. But the hydrophobic nature of mycobacterial cell walls leads to

the formation of clumps when they are resuspended in aqueous solutions. Such

aggregation may interfere in the mycobacteria interaction with the tumor cells and,

consequently, influence their antitumor effect.

To improve the immunotherapeutic activity of M. brumae, we designed different emulsions

and demonstrated their efficacy. The best formulation was initially selected based on

homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better

preserved the mycobacteria viability and provided higher disaggregation rates compared

to the other emulsions evaluated. But, among both emulsions, the OO emulsion increased

the mycobacteria capacity to trigger cytokines’ production in infected bladder tumor cell

cultures. Moreover, the OO-mycobacteria emulsion properties: less hydrophobic, lower

pH, more neutralized zeta potential, and increased affinity to fibronectin than non-

emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium

in vivo. Then, intravesical OO-M. brumae-treated tumor-bearing mice showed a

significantly higher systemic immune response, together with a trend toward increased

mice survival rates compared to the rest of treated mice.

The physicochemical characters and the induction of a robust immune response in vitro

and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the

mycobacterial treatment of bladder cancer.

16 www.sci.cat


8 Oligosaccharides activity in acute gastroenteritis of RV-infected

suckling rats

Azagra-Boronat I.1,2

; Massot-Cladera M.1,2

; Rodríguez-Lagunas M.J.1,2

; Castell M.1,2

; Franch A.1,2

; Pérez-Cano F.J.

1,2

1Department of Biochemistry and Physiology. Faculty of Pharmacy and Food Sciences. UB. Barcelona;

2Institute for Research on Nutrition and Food Safety (INSA-UB), Barcelona.

Breastfeeding has been shown to be associated with a lower incidence of rotavirus (RV)

infection in early life. In this regard, it is generally accepted that the oligosaccharides (OS)

found in breast milk are important stimulating factors for the development of the postnatal

intestinal microbiota and immune system. Because of their complexity and variability, most

infant formulas just include a few of these OS as dietary ingredients, which are obtained

from chemical or enzymatic procedures.

The aim of this study was to establish the modulatory ability of two structurally different OS

similar to those present in breast milk (OS1 and OS2) using the RV-induced diarrhea

model in Lewis suckling rats, previously set up in our laboratory.

In order to achieve this purpose, neonatal Lewis rats were supplemented with OS from the

2nd to the 16th day of life. On the 5th day of life RV was intragastrically inoculated in the

positive control group (RV) and the supplemented groups (RV+OS1 and RV+OS2). A

reference control group (REF) was not inoculated. Fecal samples were daily obtained and

evaluated in order to calculate clinical severity and incidence indicators. Viral shedding

and gut permeability were determined by ELISA. Finally, IgA-coated bacteria were

assessed by flow cytometry.

OS1 and OS2 showed amelioration in both RV severity and incidence during the peak of

diarrhea. However, the mechanism of protection seemed to be different in each case. OS1

elucidated a reduction of the detection of viral shedding and a putative binding to the RV,

probably blocking the infection process, whereas OS2 prevented the deterioration of gut

barrier integrity due to the viral replication. Moreover, OS1 reduced the IgA-coated

bacteria.

It can be concluded that both types of OS can modulate the preclinical RV-induced

diarrhea model in Lewis suckling rats by acting through different mechanisms of action..

www.sci.cat 17


9 Regulatory properties of Statins and Rho GTPases prenylation

inhibitiors to stimulate melanoma immunogenicity and promote

anti-melanoma immune response

Guillaume Sarrabayrouse1; Christine Pich

2; Iotefa Teiti

3; Anne Françoise Tilkin-Mariame

4

1Vall d'Hebron Research Institute, Passeig Vall d'Hebron, Barcelona;

2Center for Integrative genomics,

University of Lausanne, Lausanne, Switzerland.; 3Université de Toulouse, UPS

, Toulouse, France;

4INSERM

U1220, IRSD, Universitée de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.

Melanoma is a highly lethal cutaneous tumor, killing affected patients through development

of multiple poorly immunogenic metastases. Suboptimal activation of immune system by

melanoma cells is often due to molecular modifications occurring during tumor progression

that prevent efficient recognition of melanoma cells by immune effectors. Statins are HMG-

CoA reductase inhibitors, which block the mevalonate synthesis pathway, used by millions

of people as hypocholesterolemic agents in cardiovascular and cerebrovascular diseases.

They are also known to inhibit Rho GTPase activation and Rho dependent signaling

pathways. Rho GTPases are regarded as molecular switches that regulate a wide

spectrum of cellular functions and their dysfunction has been characterized in various

oncogenic process notably in melanoma progression. Moreover, these molecules can

modulate the immune response. Since ten years we have demonstrated that Statins and

other Rho GTPases inhibitors are critical regulators of molecules involved in adaptive and

innate anti-melanoma immune response. Indeed, treatments with IFN-γ and Rho GTPases

inhibitors increase the immunogenicity of melanoma cells thanks to over-expression of

MHC class I and costimulatory molecules on tumor membrane, which promote expansion

and activation of tumor specific T CD8 cytotoxic lymphocytes. In a preclinical model of

vaccination, murine melanoma cells, treated ex vivo with IFN-γ and Rho GTPases

inhibitors, induced a protection against untreated tumor growth and pulmonary metastases

implantation. Statins appear to be interesting pharmacological molecules in melanoma

therapy due to their properties to stimulate stress signal expression on melanoma cell

surface and to improve innate anti-tumor immune response. Finally, inhibitors of Rho

effectors, demonstrated also therapeutic interest. We strongly believe that all these works

argue, that inhibitors of Rho GTPases or Rho effectors, like statins that favor anti-

melanoma immune responses, could be used in the future as therapeutical drugs to

stimulate antimelanoma immune responses, alone or in association with already used

immunotherapy protocols.

18 www.sci.cat


10 Immune responses in a murine device-related infection model:

role of IL-17A

Marina Sabaté Brescó1,2

; Corina Berset1; Katharina Kluge

1; Geoff Richards

1; Fintan Moriarty

1; Liam

O'Mahony2

1AO Research Institute Davos, Switzerland;

2Swiss Institute of Allergy and Asthma Research.

Introduction: Infection associated with implanted devices is one of the major

complications of surgically fixed fractures. In this study, a murine implant-associated

infection model was established with a clinical isolate of Staphylococcus epidermidis as a

contaminating agent. The development of infection over time and associated immune

responses were assessed, with emphasis on IL-17A responses as previous studies

suggested a role in bacteria clearance.

Methods: Titanium MouseFixTM (RISystem AG, Davos) plates, with or without S.

epidermidis (104 CFU), were used to fix a femoral osteotomy in wild-type (WT) C57Bl/6

mice (female, 20-28 weeks). Mice were sacrificed at 3, 7 and 14 days after surgery (n=6-9

per group). Additionally, WT and IL-17A KO C57Bl/6 mice (female, 20-28 weeks) were

operated and sacrificed at day 14. Live bacteria from the implant, bone and soft-tissue

were quantified. Bone homogenates and supernatants of ex vivo stimulated bone cells

were collected for cytokine and chemokine quantification. Lymph node and bone cells

were characterized by flow cytometry.

Results: Three days post-operatively all WT animals were infected, with live bacteria

recovered from all samples. From day 7, no bacteria were cultured from some animals

(9/16 in total), indicating that the immune system was capable of clearing the infection.

Inoculation of bacteria was associated with an increase of inflammatory markers (such as

TNF-α or IL-6), which peaked at day 7. An increase of IL-17+ cells was detected in local

lymph nodes, especially in those animals where bacteria were cleared. When using IL-17A

KO mouse strain, it was observed that 100% of the animals remained infected at day 14

while 25% of WT cleared bacteria. However the differences were not significant,

suggesting that IL-17A partially contributes to infection clearance but other factors are also

involved. IL-17A sources in bone marrow were assessed, being predominantly CD3+CD4+

and γδ T lymphocytes.

www.sci.cat 19

Oral Communications Session III From Innate to Adaptative Immunity 11 - 15

11 Human tolerogenic dendritic cells upregulate EP2/EP3 receptors to potentiate the immunosupressive activity of PGE2.

Georgina Flórez-Grau1; Raquel Cabezón

1; Kyra J. E. Borgman

2; Carolina España

1; Daniel Benítez-

Ribas3

1Institut d'Investigacions Biomèdiques August Pi i sunyer (IDIBAPS), Barcelona, Spain;

2The Institute of

Photonic Sciences (ICFO), Castelldefels, Spain; 3Dept of Immunology, Hospital Clinic de Barcelona,

Barcelona, Spain.

Dendritic cells (DCs) are antigen presenting cells (APCs) that promote both pro- and anti-

inflammatory immune responses. Along this line, in order to treat autoimmune diseases,

generation of DCs in the presence of corticosteroids, such as dexamethasone (Dex) has

been described to generate tolerogenic DCs (tol-DCs) in vitro. Tol-DCs present a semi-

mature phenotype of costimulatory molecules, a pronounced shift towards anti-

inflammatory cytokine production and reduced capacity to stimulate T-cells response.

Prostaglandin E2 (PGE2) is crucial for the immune response as it regulates both pro and

anti inflammatory responses. Moreover it is involved in DCs maturation. PGE2 signals via 4

receptors named as EP receptors (EP1-4). However, the expression and function of EP

receptors in human tol-DCs has not been studied.

We have determined that tol-DCs upregulate EP2 and EP3 receptors.Moreover;

Interestingly PGE2 is crucial for IL-10 production by tol-DCs. In order to investigate which

EP receptor was involved in IL-10 production we treated tol-DCs with selective agonists

and antagonists of each receptor (2, 3 and 4).PGE2 signaling via EP2 or EP3 receptors

have a direct role in IL-10 production by tol-DCs. In contrast, EP4-signalling inhibits IL-10

production. Experiments using EP2 EP3 and EP4 receptors selective antagonists

confirmed our findings. Moreover we also investigate the effects of PGE2 treated tol-DCs

on T naïve cell polarization. Our results shown a bias towards IFN-γ/IL-17 double positive

T cells when tol-DCs were generated using EP4 receptor agonist.

In conclusion, herein we report that dex induces changes in the expression pattern of EP

receptors in tol-DCs. We identifiy that PGE2 signalling through EP2 or EP3 is related with

the anti-inflammatory role of PGE2 meanwhile EP4 is involved with inflammatory pathways

of PGE2 signalling.

20 www.sci.cat


12 Diving into apoptosis: liposome-based platform for autoimmune diseases

Silvia Rodriguez-Fernandez1; Irma Pujol-Autonell

1; Maria-Jose Mansilla

1; Mary Cano-Sarabia

2; Rosa-

Maria Ampudia1; Juan Navarro-Barriuso

1; Sonia GarcÍa-Jimeno

2; David Perna-Barrull

1; Cristina

Izquierdo4; Thomas Stratmann

4; Eva M. Martínez-Cáceres

1; Joan Verdaguer

1; Daniel Maspoch

2,3;

Marta Vives-Pi1

1Immunology Division, Germans Trias i Pujol Research Institute, UAB, Badalona;

2Catalan Institute of

Nanoscience and Nanotechnology (ICN2), Bellaterra; 3ICREA, Barcelona;

4Dept. of Cell Biology, Physiology

and Immunology, University of Barcelona.

Autoimmune diseases are caused by the destruction of the host’s own cells by

autoreactive lymphocytes. There are nearly 100 autoimmune diseases, with increasing

incidence and affecting around 5% of the population. Genetic and environmental factors

contribute to autoimmunity but the triggering factors remain unknown, and current

therapies are poorly effective and cause side effects. Therefore, new and safe approaches

are required to arrest autoimmunity and allow target tissue regeneration.

Based on apoptotic cells’ ability to induce self-tolerance after phagocytosis, liposomes that

possess their inherent tolerogenic features have been designed. Liposomes are

phospholipid bilayer vesicles that constitute a versatile system for modulation of immune

responses. The herein reported liposomes are made of phosphatidylcholine, cholesterol,

phosphatidylserine (PS) —the main 'eat me' signal exposed in the membrane of apoptotic

cells—, and display a diameter greater than 500 nm to promote phagocytosis.

Liposome’s ability to restore self-tolerance was tested in experimental models of

autoimmune diseases: the non-obese diabetic (NOD) mouse for type 1 diabetes (T1D),

and the experimental autoimmune encephalomyelitis (EAE)-induced mouse for multiple

sclerosis (MS). Liposomes were generated encapsulating disease-specific autoantigens:

insulin peptides for T1D and myelin-oligodendrocyte glycoprotein peptide for MS.

Liposomes were efficiently engulfed by dendritic cells, inducing a tolerogenic phenotype

and function. Liposomes were successful at arresting autoimmunity in vivo: T1D and

EAE’s incidence was decreased and their onset delayed. Moreover, EAE’s severity was

reduced. PS-Liposomes induced an antigen-specific CD4+ FoxP3+ and FoxP3– T cell

response in the T1D model, and FoxP3– T lymphocytes correlated with minor clinical signs

and hinted at belonging to Type 1 regulatory T cells in the MS model.

This work validates PS-liposomes as a powerful tool for the re-establishment of tolerance.

Working synergistically, autoantigen-loaded PS-liposomes co-deliver a double signal of

tolerance and specificity to arrest autoimmune reactions in an effective and safe manner.

www.sci.cat 21


13 The mitochondrial protein Mfn2 controls ROS production and inflammation

Juan Tur1; Selma Pereira-Lopes

1; Antonio Celada

1; Jorge Lloberas

1

1Departament de Biologia Cel·lular, Fisiologia i Immunologia. Universitat de Barcelona.

Mitochondria are well known for their role as bioenergetic and biosynthetic organelles.

Recently, they also have emerged as one of the main regulators of innate immune

responses, mostly for its ability to modulate several signaling pathways through

mechanisms such ROS production. Mitofusin-2 (Mfn2) is a GTPase located in the external

mitochondrial and ER membranes. It is responsible for the fusion between mitochondria

and the ER-mitochondria contacts, both necessary for the correct functioning of both

organelles. Even that, the role of Mfn2 in the signaling of innate immune responses is still

unknown.

Here we report that Mfn2 is crucial for the pro-inflammatory activation of macrophages.

Murine Mfn2-/- macrophages show a disrupted mitochondrial network that leads to

decreased mitochondrial membrane potential, respiration, and ROS production. The

decrease in ROS severely compromises the ability of these Mfn2-/- macrophages to

properly activate p38, ERK, and NF-κB signaling pathways, resulting in a severely

diminished production of pro-inflammatory cytokines. Furthermore, myeloid-conditional

Mfn2-/- mica exhibit a dramatically decrease in the survival against Listeria infection,

showing that Mfn2 is crucial for macrophage-mediated immune responses. Finally, sterile

inflammatory responses are also downregulated in Mfn2-/- mice, as DNFB-induced ear

irritation is reduced in these animals.

All these findings suggest that Mfn2 is a crucial regulator of macrophage pro-inflammatory

activation through modulation of mitochondrial ROS production.

22 www.sci.cat


14 The phenotipe of B lymphocytes is determinant for

autoreactive T cell activation in Type 1 Diabetes

Leire Egia-Mendikute1; Berta Arpa

1; Estela Rosell-Mases

1; Celia Vived

1; Celeste Santos

1; Conxi

Mora1; Thomas Stratmann

2; Marta Vives-Pi

3; David Serreze

4; Joan Verdaguer

1

1Immunology Unit. Department of Experimental Medicine. University of Lleida IRBLleida;

2Department of Cell

Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona; 3Immunology Department;

Institut d’Investigacio Germans Trias i Pujol. Badalona, Barcelona; 4The Jackson Laboratory, Bar Harbor,

Maine, USA.

Type 1 Diabetes (T1D) is characterized by the lost of pancreatic beta cells due to an

autoimmune process, mediated by T and B lymphocytes. Recently, we generated two B

lymphocyte transgenic mouse models, the 116C-NOD and NOD-PerIg

mice.Immunoglobulin transgenes of 116C-NOD come from the hybridoma H116, which

derives from a pancreatic islet-infiltrate of a diabetes-resistant but isulitis–prone (8.3-

NODxNOR)F1 mouse. Immunoglobulin transgenes of NOD-PerIg come from the

hybridoma H280, which derives from a pancreatic islet-infiltrate of a NOD mouse. In the

116C-NOD, disease is decelerated in both genders and there is a lower incidence of T1D

compared to the wild-type NOD mouse. In contrast, acceleration of T1D and an increase

of disease incidence are observed in both genders of NOD-PerIg compared to wild-type

NOD mouse. To understand the differences between the two transgenic models, different

lymphocyte populations were analyzed. No T lymphocyte differences were detected

between both transgenic mouse models. However, an important increase of costimulatory

molecules in spleen and isletinfiltrating B lymphocytes of NOD-PerIg was observed

compared to 116C-NOD mice. These results underline B cell status as one of the critical

factors for T1D development, and confirm the primary role of B cells in T cell activation in

T1D.

www.sci.cat 23


15 Characterization of the pulmonary and systemic immune

response in patients with Chronic Obstructive Pulmonary

Disease

Tamara Cruz1,2

; Alejandra López-Giraldo1,2

; Guillaume Noell1,2

; Marco A. Fernandez3; Alvar Agusti

1,2;

Rosa Faner1,2

1Hospital Clinic, IDIBAPS, Universitat de Barcelona;

2CIBER Enfermedades Respiratorias;

3Institut de

Recerca Germans Trias i Pujol.

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an

abnormal immune response to tobacco smoke, both in the lungs and circulating blood,

which is not fully understood. Whether or not pulmonary and systemic inflammation are

related is also unclear.

Objectives: To characterize and contrast the pulmonary and systemic immune response

in COPD patients (current smokers=33; former smokers=23) and healthy controls (current

smokers, n=15 and non-smokers, n=13).

Methods: Non-tumoral lung tissue and circulating blood were obtained from individuals

undergoing lung resectional surgery, mostly because of lung cancer. In both sample types,

flow cytometry was used to assess the immune cell composition: T and B lymphocytes, NK

cells, NKT cells, Neutrophils, Macrophages, Monocytes and Dendritic cells.

Results: In lung tissue of current smokers with COPD vs. controls we observed an

increase in the proportion of Macrophages (mainly M1-M2) and a decrease in T-

lymphocytes (mainly T CD4). In blood of these same patients vs. controls we observed

differences in the proportion of monocytes. These abnormalities were not seen in former

smokers with COPD, which in turn have increased numbers of neutrophils in lung tissue.

Finally, using network analysis we found that the in lung, but not blood, the immune cell

composition was correlated with lung function variables. A model to identify biomarkers of

the lung abnormalities in blood is currently being analysed.

Conclusions: Current smoking and presence of COPD are associated with differences in

the pulmonary immune cell response in the lungs but not in blood. This suggests that

these two compartments are independently regulated.

Supported by FIS PI12/01117, FUCAP 2013, SEPARPI192/2012 and PI065/2013

24 www.sci.cat

e-poster List

Posters Clinical Immunology 1 - 4 The authors will attend the poster on 17/11/2016: 17:30h; 18/11/2016: 11:00h, 13:30h, 16:55h.

1 Predictive biomarkers for optimal therapeutic response to

fingolimod treatment in MS patients

Bibiana Quirant-Sánchez1,2

; Aina Teniente-Serra1,2

; José Vicente Hervás3; M José Mansilla

1; Cristina

Ramo-Tello3; Eva Martínez-Cáceres

1,2

1Immunology Division. Germans Trias i Pujol University Hospital (HUGTiP) and Research Institute,

Badalona; 2Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Bellaterra;

3Multiple Sclerosis Unit, Dept. of Neurosciences. HUGTiP, Badalona.

BACKGROUND: Fingolimod (FTY720) is one of the first-line therapies for relapsing-

remitting multiple sclerosis (RRMS), which sequesters T-cells to lymph nodes through

functional antagonism of sphingosine-1-phosphate 1 receptor, thereby reducing the

number of potential autoreactive cells migrating to the central nervous system.

OBJECTIVE: To evaluate an extensive panel of leukocyte subpopulations in peripheral

blood as potencial biomarkers of therapeutic response to fingolimod.

METHODS: Longitudinal analysis of T, B, NK, monocyte and dendritic-cell subpopulations

was performed by multiparametric flow-cytometry in 45 RRMS patients at baseline and

after +1, +3, +6 and +12 months of fingolimod treatment. Data were analyzed using

Kolmogorov-Smirnov test. In case of no-normal distribution, Wilcoxon, U-Mann Whitney or

Kruskal-Wallis test were used, as appropriate.

RESULTS: Fingolimod treatment induced a severe lymphopenia affecting mainly T and B

cells. However, an relative increase of Tregs (memoryTreg: baseline: 3.8 ± 1.0 % vs

month +1: 8.8 ± 4.4 % and activatedTreg: baseline: 1.5 ± 0.7 % vs month +1: 3.7 ± 2.1 %,

p < 0.001) and transitional B- cells (baseline: 10.5 ± 12.3 % vs month +1: 18.7 ± 14.6 %, p

< 0.001) was observed. Interestingly, lymphocyte subpopulations were significantly

different in responder patients already at baseline, highlighting a lower percentage of

Recent Thymic Emigrants (responder: 4.0 ± 1.4 % vs non-responder: 7.4 ± 1.9 %, p

<0.000). Patients that suffered clinical relapses during follow-up had higher percentage of

CM CD4+ (relapsed: 36.1 ± 8.8 % vs non-relapsed: 27.2 ± 5.2 %, p <0.05) as well as

Th1Th17 (Th1Th17 TCM: relapsed: 15.4 ± 6.2% vs non-relapsed; 10.5 ± 4.1%, p < 0.05)

at baseline compared to relapse-free patients.

CONCLUSIONS: These results support that immune-monitoring of minor lymphocyte

subpopulations in peripheral blood is a powerful tool for the management of patients under

fingolimod treatment that may be extrapolable to other immunotherapies.

www.sci.cat 25


2 Modulation of Treg-IL17producing Treg cells by Adalimumab

in Psoriasis patients

María Teresa Sanz1; Miguel Sánchez

2; Silvia Vidal

1; Cándido Juárez

1; Luis Puig

2; Esther Moga

1

1Immunology Department Hospital de la Santa Creu i Sant Pau;

2Dermatology department hospital de la

Santa Creu i Sant Pau.

Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated

with IL-23, Th17 cells and impaired suppressive capacity of Foxp3+ regulatory T cells

(Tregs). Proinflammatory cytokines such as IL-23 have recently been reported to convert

Tregs into inflammation-associated IL17-producing Treg cells in psoriasis. Our working

hypothesis is that effective treatment with Adalimumab is associated with changes in

Treg/Th17 associated phenotype, reverting to the normal status.

This is a prospective follow-up post-authorization study. 20 control volunteers and 20

patients with psoriasis treated with Adalimumab were recruited. Peripheral blood samples

were collected before the treatment (w0), at 4 (w4) and 16 (w16) weeks after initiating the

treatment and on one occasion in healthy volunteers. Peripheral blood mononuclear cells

(PBMCs) were isolated and Th17, Treg and IL17-producing Treg populations were

analyzed by flow cytometry using surface and intracellular markers, after incubation with

IL-2 or IL-2 and IL23 during 5 days.

The results obtained show that IL23 increases Treg (CD4+CD25+FoxP3+cells)

differentiation into IL-17-producing Tregs (CD4+CD25+FoxP3+IL17+cells) in both control

and psoriasis patients at w0. This increase is significantly higher in patients at w0 than in

controls. Moreover, patients at w0 show a decrease in the percentage of Treg and an

increase in Th17 (CD4+IL17+cells) population when compared with controls. In order to

simplify this methodology, we replaced intracellular markers Foxp3 and IL17 by surface

markers CD127 and CD161. Psoriasis patients at w0 show a decrease in Treg population

(CD4+CD25+CD127-cells) and an increase in Th population with potential capacity to

produce IL17 (CD4+CD161+cells) compared with controls.

On the other hand, treatment tends to decrease the percentage of IL17-producing Tregs in

Psoriasis patients at w4 and w16.

In conclusion, clinical improvement of Psoriasis patients treated with Adalimumab is

associated with normalization in thebalance Treg/IL-17-producing Tregs.

26 www.sci.cat


3 Genetic and experimental evidence on the involvement of the

CD6 lymphocyte receptor in psoriasis

Marta Consuegra-Fernández1; Marc Julià

2; Mario Martínez-Florensa

1; Fernando Aranda

1; Noelia

Armiger-Borràs1; María Teresa Arias

3; Francisca Santiago

3; Antonio Guilabert

4; Anna Esteve

5; Carlos

Muñoz4; Carlos Ferrándiz

6; José- Manuel Carrascosa

6; Edurne Pedrosa

7; Jorge Romaní

8; José

Manuel Mascaró-Galy9; Francisco Lozano

1,3,10

1Immunoreceptors del Sistema Innat i Adaptatiu, IDIBAPS, Barcelona.;

2Servicio de Dermatologia, Hospital

Universitario de Basurto, Bilbao.; 3Servei d’Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de

Barcelona; 4Servei de Dermatologia, Hospital General de Granollers, Barcelona;

5Centre d’Estudis

Epidemiològics sobre les ITS i SIDA de Catalunya (CEEISCAT), ASPC, CIBER; 6Servei de Dermatologia,

Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona.; 7Laboratori d’Immunobiologia, Institut

d’Investigació en Ciències de la Salut Germans Trias i Pujol.; 8Servei de Dermatologia, Consorci Sanitari

Parc Taulí, Universitat Autónoma de Barcelona, Sabadell; 9Servei de Dermatologia, Hospital Clinic de

Barcelona; 10

Unitat d’Immunologia, Departament de Biomedicina, Facultat de Medicina, Universitat de

Barcelona.

CD6 is an inmunomodulatory lymphocyte receptor recently proposed as a putative

therapeutic target in some autoimmune diseases. Although several independent clinical

studies have exhibited efficacy of a humanized anti-CD6 monoclonal antibody in the

treatment of psoriasis, no evidence has been reported regarding the underlying

mechanisms implicating CD6 in the pathophysiology of such a disease. Here we analyzed

the immune responses of CD6-deficient (CD6-/-) mice of C57BL/6 background undergoing

the experimental psoriasis model induced by imiquimod (IMQ). The results show that CD6-

/- mice present an attenuated form of IMQ-induced psoriasis compared to wild-type

C57BL/6 mice, as deduced from diminished epidermal hyperplasia and levels of

intralesional inflammatory cytokines. Further evidence on the involvement of CD6 in

psoriasis was obtained in an observational study analyzing the clinical relevance of an

intronic polymorphism of the CD6 gene previously linked to enhanced susceptibility to

multiple sclerosis. The analysis of a cohort of 304 patients who have moderate to severe

psoriasis and 305 healthy controls from three general hospitals of the Barcelona’s area

(Hospital Clínic of Barcelona, Hospital Germans Trias i Pujol and Consorci Sanitari Parc

Taulí), revealed a significant association between the minor allele and early onset and

higher severity of the disease. Taken together, the present findings provide new genetic

and in vivo experimental evidence highlighting the relevance of CD6 in the

pathophysiology of psoriasis.

Work supported by the Spanish Ministerio de Economía y Competitividad (SAF2013-

46151-R), cofinanced by European Development Regional Fund “A way to achieve

Europe” ERDF.

www.sci.cat 27


4 PD1 and PD-L1 expression in Graves’ disease thyroid tissue. A

clue to better understand thyroid immunopathology?

Daniel Alvarez de la Sierra1,2

; de Jesus Gil C.1,2,3

; Lucas-Martin A.6,7,8

; Obiols G.4; Caragol I.

1; Ferrer

R.9; Gonzalez O.

5; Casteras A.

4; Pujol Borrell R.

1,2,3

1Immunology Division, Hospital Universitari Vall d'Hebron (HUVH);

2Vall d'hebron Institut de Recerca (VHIR);

3Departament of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona;

4Endocrinology Division, HUVH;

5Surgery Division, HUVH;

6Endocrinology Division, Hospital Universitari

Germans Trias i Pujol; 7Departament of Medicine, Universitat Autonoma de Barcelona;

8Institut de

Investigació en Ciències de la Salut Germans Trias i Pujol, IGTP; 9Clinical Chemistry Division, HUVH.

In Graves' disease (GD) thyroid follicular cells (TFC) overexpress HLA class I and class II.

In spite of being described over 30 years ago, the consequences of this hyper expression

of HLA in TFCs remains speculative. In GD, TFC also express increased level of ICAM-1

and CD40 but whether they express PD-1L that may inhibit T cells is not known.

Interestingly both GD and hypothyroidism have been observed in patients treated with

anti-PD1. The analysis of the expression and distribution of inhibitory molecules (immune-

checkpoint molecules) may help understand the immune response in GD and the

triggering of thyroid autoimmunity in cancer patients treated with MoAbs to Immune Check

Point molecule PD-L1.

Cryostat sections of GD, MNG and lymphoid control tissue were stained by IFL for PD-1,

PD-L1, LAG-3 as well as HLA, lymphocyte markers, Cytokeratin-18 and TPO. Primary

TFC and HT93 thyroid cell cultures were supplemented with increasing doses of IFN-

gamma and stained at 48h-72h to assess HLA and PD-1L induction.

In 11 out of 12 GD glands PD-L1 was detected in TFC. PD-L1 staining was, however,

confined to a few follicles close to lymphoid infiltrates and was much less extensive than

HLA class II. In MNG only traces of PD-L1 staining was visible in TFCs. Importantly, PD1

was highly expressed by the infiltrating T cells in GD. By analogy with tumoral tissue, PD-

L1+ TFCs in GD glands could actually inhibit T cells counterbalancing the effect of HLA

and adhesion molecules. PD-L1 expression was induced by IFN-gamma in cultured TFC

as HLA. LAG3 staining was observed in rare scattered cells through the infiltrating

lymphocytes. Further work is required to confirm and support both the histopathological

findings and the functional implications. These data may also help to understand the

frequent occurrence of GD and hypothyroidism in patients treated with anti-PD1.

28 www.sci.cat

Posters Diagnostic Immunology 5 - 9 The authors will attend the poster on 17/11/2016: 17:30h; 18/11/2016: 11:00h, 13:30h, 16:55h.

5 IL1R1 as a biomarker of vitamin D3-tolerogenic dendritic cells

Aleix Rius-Rigau1,2

; María José Mansilla1,2

; Juan Navarro-Barriuso1,2


; Bibiana Quirant-Sánchez

1,2; Silvia Presas-Rodríguez

3; Alex Sánchez

4; Cristina Ramo-Tello

3; Eva M. Martínez-

Cáceres1,2

1Division of Immunology, Germans Trias i Pujol Research Institute (IGTP);

2Department of Cellular Biology,

Physiology and Immunology, Universitat Autònoma de Barcelona; 3Multiple Sclerosis Unit, Department of

Neurosciences, Germans Trias i Pujol University Hospital; 4Statistics Department, Faculty of Biology,

University of Barcelona.

Background: Autologous therapy withtolerogenic dendritic cells (tolDC) loaded with

autoantigens is a promising strategy for autoimmune diseases. In order to translate this

therapy, specific biomarkers of potency are required as quality control before cell infusion

to patients. From a microarray analysis comparing vitamin D3-tolDC to immature (iDC) and

mature DC (mDC), IL1R1 gen was found downregulated in vitD3-tolDC compared to iDC

and mDC.

Objective: To validate IL1R1 as a biomarker of vitD3-tolDC.

Methods: TolDC were obtained after 6 days of culture of healthy donor’s peripheral blood

monocytes in presence of IL-4, GM-CSF and vitD3. The last 48h, tolDC were stimulated

with IL-1β, TNFα and PGE2 to induce maturation. In parallel, mature DC (mDC) were

obtained from cultures without vitD3, and immature DC (iDC) from cultures without either

vitD3 orcytokine cocktail. Characterization of gene and protein expression of IL1R1 in iDC,

mDC and tolDC was performed by qPCR and flow cytometry, respectively.

Results: Microarray results were validated in 24 differentiations from healthy donors.

Compared to iDC, mDC exhibited increased levels of IL1R1 (p<0.01) either at gene or

protein level. Interestingly, the treatment with vitD3 reduced gene (p<0.001) and protein

expression (p<0.01) of IL1R1 compared to both, mDC and iDC. To analyse the role of IL-

1β in DC maturation, DC were differentiated without IL-1β and analysed phenotypic- and

functionally (n=11). The absence of IL-1β in the maturation cocktail reduced CD86

expression (p=0.028) and slightly the allogeneic proliferation (p=0.08) of mDC.

Conclusion: IL1R1 downmodulation induced by vitD3 may contribute in part to the

downmodulation of CD86, but other molecules are necessary to confer the tolerogenic

function to these cells.

www.sci.cat 29


6 Validation of CAMP as a potential biomarker for a vitamin D3-

induced tolerogenic dendritic cell-based therapy in multiple

sclerosis

Juan Navarro-Barriuso1,2

; María José Mansilla1,2

; Aleix Rius-Rigau1,2


; Bibiana Quirant-Sánchez

1,2; Silvia Presas

3; Alex Sánchez

4; Cristina Ramo-Tello

3; Eva María Martínez-

Cáceres1,2

1Division of Immunology, Germans Trias i Pujol Research Institute (IGTP);

2Department of Cellular Biology,

Physiology and Immunology, Universitat Autònoma de Barcelona; 3Multiple Sclerosis Unit, Department of

Neurosciences, Germans Trias i Pujol University Hospital; 4Statistics Department, Faculty of Biology,

University of Barcelona.

Background: A breach of tolerance against determined self-peptides may lead to a

complex and pathologic disorder of the immune system, causing autoimmune diseases

such as multiple sclerosis (MS). Novel autologous vitamin D3-induced tolerogenic dendritic

cell (vitD3-tolDC)-based therapies have become promising therapeutic alternatives to

conventional treatments for autoimmune diseases by their potential ability to restore

tolerance against the peptide they present. In order to guarantee the safety and

tolerogenicity of vitD3-tolDC prior to administration into patients in a clinical trial, it is

important to have robust biomarkers. In this context, the CAMP gene, encoding the

cathelicidin antimicrobian peptide, which develops several functions such as immune

mediators induction and inflammatory response regulation, could be a good candidate.

Objective: To validate CAMP as a potential biomarker to characterize vitD3-tolDC

differentiated from monocytes from both healthy donors (HD) and MS patients.

Methods: To validate CAMP as differentially expressed in vitD3-tolDC, compared to both

immature (iDC) and mature dendritic cells (mDC), 24 monocyte-derived dendritic cell

differentiations of iDC, mDC and vitD3-tolDC from healthy donors and 6 from MS patients

were generated and characterized phenotypically and functionally (inhibition of allogeneic

peripheral blood mononuclear cells). RNA was extracted and retrotranscribed into cDNA,

and the expression of CAMP was analyzed by qPCR, using GAPDH, TBP and CYPA

genes as endogenous controls. Expression was considered differential when logFC>0.5.

Results: In HD, CAMP was overexpressed in vitD3-tolDC compared to mDC (logFCHD

0.96±0.15), while the mean expression between iDC and mDC remained unchanged

(logFC<0.5). The same behavior was observed in patients (logFCpatients 0.61±0.30).

Statistical significance was reached in both cases (p<0.05).

Conclusions: The results suggest that CAMP may be a robust biomarker to characterize

vitD3-tolDC products. Nevertheless, although already validated in HD, sample size should

be increased in order to confirm this in MS patients.

30 www.sci.cat

Posters Diagnostic Immunology 5 - 9

The authors will attend the poster on 17/11/2016: 17:30h; 18/11/2016: 11:00h, 13:30h, 16:55h.

7 Faecal calprotectin as a biomarker of intestinal graft versus

host disease after allogeneic hematopoietic stem-cell

transplantation

Mireia Fonolleda Ramboux1; Àlex Soriano Martínez

1; Bibiana Quirant-Sánchez

1; Eva M. Martínez-

Cáceres1; Aina Teniente-Serra

1

1Immunology Division, Hospital Universitari Germans Trias i Pujol.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (aHSCT) is a

potentially curative treatment for patients with malignant and non-malignant diseases.

Approximately 40-50% of patients receiving allogeneic grafts suffer from gastro-intestinal

graft-versus-host-disease (GI-GvHD). This condition cannot be diagnosed accurately

based on clinical symptoms, requiring endoscopic examination and biopsy. Faecal

calprotectin (FC) is a sensitive marker of disease activity in inflammatory bowel disease.

Recent data support its utility to differentiate lower GI-GvHD from other disorders such as

infection or mucosal damage due to conditioning therapy.

OBJECTIVE: To analyze retrospectively the correlation between FC concentration and

clinical grade of lower GI-GvHD.

MATERIALS AND METHODS: Nine patients (7 male, 2 female) with suspicion of lower

GI-GvHD after aHSCT were included. Median age was 45 (range 19-67). Key symptoms

considered for lower GI-GvHD were: abdominal pain, diarrhea, rectorrhagia and ileus.

Stool samples were collected at the moment of GI-GvHD suspicion on clinical grounds. FC

was assayed by ELIA (EliA Calprotectin, Thermo Scientific). CMV, adenovirus, rotavirus

and Clostridium difficile infections were excluded.

RESULTS: Patient characteristics are summarized in Table 1. Diagnosis was confirmed

histologically by endoscopicbiopsy in 8 of 8 patients. One patient also suffered from

infectious colitis confirmed by serum positive PCR for CMV. GI-GvHD grade at diagnosis

were Iº=1, IIº=1, IIIº=3, IVº=3. FC median value was 2467 mg/kg (range: 777 - >3000).

Clinical grade of GI-GvHD correlated with FC concentration (r=0.87, p=0.0007). FC levels

were higher in patients with clinical stage III-IV, with a median value of 2857 mg/kg (range:

2322 - >3000), compared with grades I-II, with a median value of 1297 mg/kg (range: 777 -

1817)(p= 0.0357).

CONCLUSIONS: Powered by Results of this preliminary study support that FC

concentration in patients with lower GI-GvHD after aHSCT is a useful marker of severity of

the disease. Further studies are necessary to confirm this finding.

www.sci.cat 31


8 Behaviour of antibodies against aquaporin-4 in a SLE patient

with an outbreak of longitudinally extensive transverse

myelitis

Andrés Baucells de la Peña1; Anaís Mariscal Rodríguez

1; M. Carmen Hernández Lafuente

1; Elisabeth

Moltó Lacosta1; Luis Querol

2; Ivan Castellví

3; Cándido Juárez Rubio

1; Laura Martínez Martínez

1

1Immunology Department, Hospital de Sant Pau;

2Neurology Department, Hospital de Sant Pau;

3Rheumatology Department, Hospital de Sant Pau.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that

affects multiple systems, including central nervous system. Neuromyelitis optica (NMO) is

associated with autoantibodies that target aquaporin-4 (AQP4). The main symptoms of

NMO, longitudinally extensive transverse mielitis (LETM) and optic neuritis, can also occur

in the context of established rheumatologic diseases, such as SLE and Sjogren syndrome

(SS). In a first episode of LETM, anti-AQP4 predicts a recurrence of a 60% within the first

year. SLE criteria do not include anti-AQP4 antibodies detection in case of myelitis. Thus,

several authors highlight the importance of determinating anti-AQP4 antibodies in these

patients due to their prognostic and therapeutic value.

Material and Methods: We reported a female patient who debuted in 2010 with a LETM

episode in a context of multiple systemic rheumatologic diseases including SLE and SS.

The patient presented anti-Ro and anti-phospholypid antibodies. Rituximab® was

administered in order to treat the dysesthesias, being successful. Later on, in 2015 she

had a new outbreak of LETM, so a second cycle of Rituximab® was administered.

Autoantibodies against anti-AQP4 were determined before and after this second cycle.

Results: The patient presented anti-AQP4 antibodies at the beginning of the second

outbreak of the myelitis. Four months after Rituximab® treatment, anti-AQP4 antibodies

became negative but the patient didn’t improve. Six months post- Rituximab®, the

symptoms began to disappear. At twelve months’ time, in coincidence with the increase of

B lymphocytes and immunoglobulins, anti-AQP4 antibodies reappeared, but the patient

remained without neurologic symptomatology.

Conclusion: The second treatment with Rituximab® in our patient leaded to the

disappearance of the anti-AQP4 before the clinical improvement. Unfortunately, we don’t

know their behaviour during the first cycle. The recovery of B lymphocytes and the

appearance of anti-AQP4 autoantibodies lead us to consider new strategies because she

is clinically asymptomatic.

32 www.sci.cat


9 Breast cancer case associated with anti-titin antibodies

Anaís Mariscal Roríguez

1; Andrés Baucells de la Peña

1; Elisabeth Moltó Lacosta

1; M. Carmen

Hernández Lafuente1; Luis Querol

1; Silvana Novelli

1; Esther Moga Naranjo

1; Cándido Juárez Rubio

1;

Laura Martínez Martínez1

1Hospital de la Santa Creu i Sant Pau.

Introduction. Paraneoplastic syndromes are signs and symptoms caused by cancer that

involve organs and tissues remote from the malignant neoplasm or its metastases. Some

of them affect to the central nervous system and are called paraneoplastic neurological

syndromes (PNS). Most PNS are immune mediated and autoantibodies are helpful when

clinical suspicion of a PNS is present. Autoantibodies against titin are mainly associated

with thymoma in myasthenia gravis (MG) patients. However, two patients with PNS

positive for anti-titin antibodies but without MG or thymoma have been recently reported.

One has breast cancer and presented chorea as PNS with anti-Ri antibodies. The other

patient was diagnosed of small cell lung cancer, presented sensorimotor neuropathy and

subacute cerebellar degeneration. She was positive for anti-CV2 and anti-CRMP5

antibodies.

Methods. We present a 73-year-old woman diagnosed of breast cancer in 2004 and

monoclonal gammopathy of undetermined significance (MGUS) IgM in 2012. Later, in

2016, the patient presented impaired peripheral sensitivity and the screening for

paraneoplastic antibodies was performed.

Results. The patient presented autoantibodies IgG against titin protein. Accordingly, she

was positive for anti-striated muscle antibodies. Reactivity for Yo, Hu, Ri, Tr, Ta/Ma2,

amphiphysin, CV2, recoverin, SOX1, titin, ZIC4 and GAD65 recombinant proteins was

negative. Indirect immunofluorescence against monkey brain and cerebellum was also

negative. Increasing levels of IgM has been observed in this last year.

Conclusions. We report a patient with breast cancer and MGUS IgM with anti-titin IgG

antibodies. Intriguingly, breast cancer was diagnosed years before PNS symptoms. Our

patient differs from the previously reported case in the absence of classical onconeuronal

antibodies. It is difficult to establish if antititin antibodies are predictors of recurrence or

metastasis of the breast cancer, or of risk of MGUS transformation to a malignant disorder.

Clinical relevance of anti-titin antibodies in this patient needs to be more evaluated.

www.sci.cat 33

Posters Immune Response 10 - 15 The authors will attend the poster on 17/11/2016: 17:30h; 18/11/2016: 11:00h, 13:30h, 16:55h.

10 Failure of mesenchymal stem cells to protect xenogeneic

porcine chondrocytes from immune rejection in the rat joint

Maribel Marquina1; Javier A. Collado

*1; Magdiel Pérez-Cruz

*1; Pablo Fernández-Pernas

2; Francisco J.

Blanco3; Rafael Máñez

1; María C. Arufe

2; Cristina Costa

1

1Infectious Diseases and Transplantation Division, IDIBELL, L'Hospitalet de Llobregat, Spain; 2Department of Medicine, INIBIC & Universidade da Coruña, A Coruña, Spain; 3Servicio de

Reumatología, INIBIC & Universidade da Coruña, A Coruña, Spain. (*Equal contributors).

Background. Current therapies do not provide a cure for most patients with cartilage

defects produced by traumatism or disease. Notably, cellular therapies may become a

solution for articular cartilage repair if the appropriate cell type is utilized. Here, we

consider the use of xenogeneic chondrocytes for cartilage repair and allogeneic

mesenchymal stem cells (MSC) for immune modulation.

Methods. A discordant xenotransplantation model was established by injecting three

million porcine articular chondrocytes (PAC) into the femorotibial joint of Lewis rats. The

immune response was monitored over time. The immunoregulatory effect of systemic

administration of bone marrow-derived MSC obtained from Wistar rats was assessed in

this model.

Results. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a

peak at week 2 post-injection and reactivity remaining above baseline levels by week 18.

IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. Consistent with a

cellular immune response to PAC, a distinct cytokine/chemokine profiling was revealed in

serum by antibody array relative to controls. This was characterized by elevation of

multiple markers at week 2 (i.e. IL-2, L-selectine), as well as increases in cell numbers in

draining lymph nodes. Interestingly, IL-2 measurements in co-cultures of rat peripheral

blood lymphocytes (PBL) with PAC indicated that PAC injection induced some T-cell

hyporesponsiveness. However, allogeneic MSC administered systemically 3 weeks after

PAC injection (intraperitoneal route) did not diminish the immune response. Tolerance was

not enhanced in the cohort additionally receiving MSC.

Conclusions. Despite the immune privilege provided by the joint and chondrocytes, PAC

injected intraarticularly in rats induced a cellular and humoral immune response. This

effect was not counteracted by systemic administration of MSC.

34 www.sci.cat

Posters Immune Response 10 - 15


11 Effect of prenatal betamethasone exposure in Type 1 Diabetes

David Perna-Barrull1; Anna Gieras

2; Rosa Maria Ampudia

1; Arnau Serracant-Prat

2; Silvia Rodriguez-

Fernandez1; Christina Gehbauer

2; Irma Pujol-Autonell

1; Eva Tolosa

2; Marta Vives-Pi

1

1Immunology Division, Germans Trias i Pujol Research Institute, UAB, Badalona, Spain;

2Department of

Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Type 1 diabetes (T1D) is an autoimmune disease against insulin-producing pancreatic β

cells. This attack decreases the capacity to synthetize insulin, tying the subject to

exogenous insulin administration to maintain normoglycaemia. The incidence of the

disease is increasing, and children and adolescents are the most affected groups.

It is believed that autoimmunity begins in the foetus, therefore using drugs during

pregnancy can alter the immune response. Betamethasone is a synthetic glucocorticoid

with anti-inflammatory and immunosuppressive abilities used in pregnant women with risk

of preterm delivery to aid in the development of foetal lungs. Moreover, betamethasone

could also affect immune system cells.

Our hypothesis is that betamethasone affects the development of the prenatal immune

system, thus influencing the risk of T1D in adulthood. The main goal is to determine the

effect of betamethasone on T1D incidence and on immune system cells.

To that end, we administered betamethasone to pregnant non-obese diabetic (NOD) mice,

the experimental model of T1D. We observed a decrease in the incidence of T1D in the

female offspring -but not in maleswhen compared to the offspring of sham mice, as well as

a delay in the clinical onset of the disease. The degree of islet leukocyte infiltration -

insulitis- was lower in both genders. To assess the direct effect of betamethasone on

immune system cells, we cultured splenocytes with this drug. Betamethasone showed

toxic effects on non-stimulated lymphocytes and induced a tolerogenic phenotype in

dendritic cells with the capacity to inhibit γδ T cell proliferation.

In conclusion, betamethasone reduces the incidence of T1D in concordance with the

insulitis score and with the in vitro results. Although further studies are needed to elucidate

the effect of betamethasone on autoimmune reactions, as well as in β cell metabolism, our

work highlights the importance of glucocorticoids in foetal immune system.

www.sci.cat 35


12 Intestinal intraepithelial lymphocyte composition is modulated

by leptin and adiponectin supplementation in suckling rats

Grases-Pintó B.1,2

; Abril-Gil M.1,2

; Rodríguez-Lagunas M.J.1,2

; Castell M.1,2

; Pérez-Cano F.J.1,2

; Franch, A.

1,2

1Department of Biochemistry and Physiology. Faculty of Pharmacy, University of Barcelona.;

2Nutrition and

Food Safety Research Institute (INSA-UB), Barcelona, Spain.

The development of the immune system begins during pregnancy and acquires its defence

capability against pathogens in the postnatal period. Many bioactive components in breast

milk such as growth factors, nucleotides and adipokines may contribute to the immune

maturation in early life. Leptin and adiponectin are metabolic hormones or adipokines

found in breast milk with immunoregulatory properties. However, the particular role of

these adipokines on neonatal immunity remains still unexplored.

The aim of this study was to determine the age-related changes on the intestinal

intraepithelial lymphocyte (IEL) composition during the suckling period and also to

establish the influence of the adipokine supplementation of rats on that IEL maturation

process.

For this purpose, suckling Wistar rats were daily supplemented by oral gavage with leptin

or adiponectin throughout all the suckling period (three weeks). On days 14 and 21, IEL

were isolated from the distal small intestine and lymphocyte composition was established

by immunofluorescence staining and flow cytometry analysis.

In suckling rats, NK cells were the main population in IEL (» 50%), followed by NKT,

TCRγδ+ and TCRαβ+ cells. NK cells changed from a typical systemic phenotype,

expressing CD8 (day 14), to a specific intestinal phenotype, lacking CD8 molecule (day

21). During this period, a decrease was observed in the NKT cell proportion, whereas a

tendency to increase of the TCRγδ+ proportion was found. The supplementation with leptin

or adiponectin along the whole suckling period increased the proportion of the IEL TCRαβ+

and NKT cells, in comparison with rats receiving vehicle.

These results show age-related changes in the composition of IEL during the last week of

the suckling period. Moreover, the nutritional supplementation of rats with leptin or

adiponectin modifies the intraepithelial lymphocyte composition, suggesting a modulatory

role of these adipokines on the intestinalimmune system development.

36 www.sci.cat



13 Gut-associated lymphoid tissue in orally sensitized rats fed a

cocoaenriched diet

Mariona Camps-Bossacoma1,2

; Francisco J. Pérez-Cano1,2

; Àngels Franch1,2

; Margarida Castell1,2

1Section of Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona;

2Nutrition and

Food Safety Research Institute (INSA-UB).

Previous studies have attributed a nutraceutical function to a diet containing 10% cocoa in

a rat oral sensitization model because it was able to prevent antibody synthesis.

The purpose of the current study was to establish the influence of a similar cocoa-enriched

diet on gutassociated lymphoid tissue, in particular, intraepithelial lymphocyte (IEL)

composition in orally sensitized rats.

Lewis rats were sensitized with oral administration of ovalbumin (OVA) plus cholera toxin

(CT) (3 times/week, 3 weeks). In this period, rats were fed either standard diet or 10%

cocoa diet. After 28 days, small intestines were collected, IEL were analysed by flow

cytometry and the gene expression of several molecules was established. Additionally, IgA

concentration in faecal samples was determined.

Oral immunization did not modify the main lymphocyte subsets in the epithelial

compartment although a decrease in the percentage of CD8+CD103+ IEL and an increase

in that of CD8+CD62L+ and CD4+CD62L+ IEL was observed. On the other hand, cocoa

enriched-diet increased the percentage of TCRγδ+ and NK cells and decreased that of

TLR4+ IEL. Moreover, lower percentage of TCRαβ+ lymphocytes was observed in OVA-

sensitized animals fed cocoa diet. Likewise, cocoa diet produced an increase in the

proportion of CD4+CD103+ cells.

On the other hand, oral sensitization induced lower intestinal IL-10 gene expression and

cocoa diet inhibited intestinal IgA synthesis (mRNA and protein) and reduced the gene

expression of CD11b, CD11c, TGF-β1 and IL-10.

In conclusion, a 10% cocoa diet induces changes on IEL composition as well as the gene

expression of several molecules in rat intestinal tissue suggesting that these changes may

contribute to enhance oral tolerance. In addition, the decrease in the gene expression of

IgA and TGF-β1 and in the proportion of TLR4+ IEL due to cocoa diet can be associated

with a decrease in the intestinal IgA production.

www.sci.cat 37


14 The human soluble form of CD5 protects mice from septic

shock caused by fungal infections

María Velasco de Andrés1; Mario Martínez-Florensa

1; Cristina Català

1; Inês Simões

1; Esther

Carreras1; Nuria Trevijano-Contador

2; Oscar Zaragoza

2; Francisco Lozano

1,3,4

1Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS);

2Centro Nacional de Microbiología;

3Hospital Clínic;

4Universitat de Barcelona.

Sepsis is an unmet clinical need that represents an important cause of world-wide

mortality. Even though bacteria are the main organisms responsible of sepsis, invasive

fungal infections are an increasingly frequent etiology of sepsis in critically ill patients

causing substantial morbidity and mortality. Previous studies by our group have shown

that a soluble form of the human lymphocyte surface receptor CD5 (shCD5) binds to and

aggregate a wide array of pathogenic and saprophytic fungal cell species through

recognition of β-glucans, a conserved structural component of fungal surfaces.

Accordingly, the i.p. infusion of recombinant shCD5 protein showed protective effects in

inbred C57BL/6 mice undergoing the experimental model of fungal sepsis induced by

Zymosan –a ß-glucan-rich yeast cell wall extract.In this work we further show the

beneficial prophylactic and therapeutic effects of recombinant shCD5 infusion to outbred

CD1 mice undergoing fungal sepsis induced by two pathogenic species, namely Candida

albicans and Cryptococcus neoformans. Time- and dose-response experiments show

statistically significant therapeutic effects of i.p or i.v. infused recombinant shCD5 on

mouse survival, macrophage and neutrophil blood counts, and serum levels of pro- and

anti-inflammatory cytokines following i.v. C. albicans and C. neoformans infection.

Altogether, our results support the therapeutical value of shCD5 administration in clinically

relevant fungal infections.

Work supported by the Spanish Ministerio de Economía y Competitividad (SAF2013-

46151-R) and Instituto de Salud Carlos III (Spanish Network for Research in Infectious

Diseases, RD12/0015/0018), cofinanced by European Development Regional Fund “A

way to achieve Europe” ERDF.

38 www.sci.cat



15 Effect of growth factors supplementation on the antibody

immune response in suckling rats

Torres-Castro P.1,2

; Grases-Pintó B.1,2

; Rodríguez-Lagunas M.J.1; Castell M.

1,2; Pérez-Cano F.J.

1,2;

Franch A.1,2

1University of Barcelona;

2Nutrition and Food Safety Research Institute (INSA-UB).

Just after birth, the immune response is deficient and less competent compared with

adults. Breast milk provides large number of compounds that contribute to the maturation

of the immune system in early life such as particular growth factors. The current study

aimed to evidence the influence of transforming growth factor β2 (TGFβ2), epidermal

growth factor (EGF) and fibroblast growth factor 21 (FGF21), present in breast milk, on the

postnatal ability for antibody production. For this purpose, newborn Wistar rats were

randomly distributed into four experimental groups: Reference, TGFβ2, EGF and FGF21

groups. Rats were daily supplemented by oral gavage with TGFβ2, EGF or FGF21 during

the first three weeks of life. At days 14 and 21, plasma samples were collected and IgA,

IgM and IgG, as well as IgG1, IgG2a, IgG2b, IgG2c isotypes, were quantified.

Results demonstrated that all experimental supplementations (with TGFβ2, EGF and

FGF21) increased the synthesis of IgG at both 14 and 21 days. Specifically, IgG1 and

IgG2a production (Th2-related antibodies in rats) was increased without affecting IgG2b

and IgG2c synthesis (Th1-related antibodies in rats). Overall, the FGF21 and TGFβ2

supplementations caused a significant decrease on the Th1/Th2 antibody pattern ratio at

day 21 compared to the reference group, being this effect also evident at day 14 in the

FGF21 group (p<0.05). No influence due to growth factors supplementation was found

regarding IgA and IgM production. These results evidence that TGFβ2, EGF and FGF21

are crucial factors in the humoral immune response in early life.

www.sci.cat 39

Posters Innate Immunity 16 - 19


16 Analysis of the neutrophil function in the ascitic fluids from

patients with decompensated cirrhosis

Lídia Perea1,3,4

; Juan Camilo Nieto1,3,4

; Elisabet Sánchez2,3,4,5

; Cristina Romero2; Eva Román

2,3,4,5;

Maria Poca2,4

; Carlos Guarner2,3,4,5

; Cándido Juárez1,3,4

; Germán Soriano2,3,4,5

; Silvia Vidal1,3,4

1Department of Immunology, Hospital de la Santa Creu i Sant Pau (HSCSP), Barcelona, Spain;

2Liver

Section, Department of Gastroenterology, HSCSP, Barcelona; 3Institut de Recerca IIB-Sant Pau, Barcelona,

Spain; 4Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain;

5Centro de

Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas.

Background: Patients with decompensated cirrhosis have complications such as

spontaneous bacterial peritonitis (SBP) that lead to a defective immune response. One of

these defects could be the described impaired functionality of ascitic neutrophils from

patients with SBP. This defect could be induced by the content of the ascitic fluid.

Aims: (a) To compare the effect of sterile ascitic fluids (SA) and SBP ascitic fluids (culture-

negative, CN-SBP or culture-positive, CP-SBP) on the function of neutrophils (oxidative

burst activity and NETosis) (b) To compare the effect of SBP ascitic fluid at the day of

diagnosis and after the antibiotic treatment on neutrophil function

Materials and Methods Patients: Ascitic fluid samples from cirrhotic patients with SBP

(n=11; 7 PosC-SBP and 4 NegC-SBP) SA (n=13). Human neutrophil isolation and

culture: Neutrophils were isolated from peripheral blood of donors using Ficoll-Hypaque,

dextran-sacarose gradient and a process of lysis. Neutrophils were cultured in a

conditioned medium with 10% of fetal calf serum (FCS) or with cell-free SA, CN-SBP and

CP-SBP. Oxidative Burst: Monitored by the oxidation of dihydrorhodamine 123 to

rhodamine by flow cytometry (MFI) in presence or absence of 320 nM PMA. NET

induction and visualization: Neutrophils were seeded on poly-L-lysine-coated coverslips

with NET medium and stimulated with 200 nM PMA for 2 hours at 37ºC 5% CO2.

Neutrophils were stained with mouse anti-human CD66b and NETs were visualized using

100 nM Sytox Green. NET quantification: Fluorescence of NET-bound Sytox Green

(excitation: 510, emission: 550) was quantified with the infinite F200 microplate reader and

Tecan i-control 1.8 software. Statistical analysis: t-Test student for paired and unpaired

data and Pearson test to analyze correlations.

40 www.sci.cat

Posters Innate Immunity 16 - 19 The authors will attend the poster on 17/11/2016: 17:30h; 18/11/2016: 11:00h, 13:30h, 16:55h.

17 Phenotypic characterizacion of myeloid-derived suppressor

cells in patients with chronic HCV infection

Elisabet Coves2; Marta Parés

2; Silvia Casacuberta-Serra

2; Marta Bes

1; Mireia Parés

1; Sergio López-

Estévez2; Silvia Sauleda

1; Juan Ignacio Esteban

3; Jordi Barquinero

2

1Banc de Sang i Teixits (BST);

2Vall d'Hebron Institut de Recerca (VHIR);

3Hospital Universitari Vall d'Hebron

(HUVH).

Myeloid-derived suppressor cells (MDSCs) accumulate in patients with cancer and chronic

inflammation and suppress adaptive immune responses. Individuals with chronic infection

with hepatitis C virus (HCV) have higher proportions of monocytic (M)-MDSCs in

comparison to age and sex matched healthy individuals. In the present study we

measured the frequencies of MDSCs in the PB of 31 HCV infected patients and 30 healthy

controls (blood donors), and we characterized these cells phenotypically. To this end,

fresh whole PB samples were stained with two different panels of monoclonal antibodies,

that included extracellular markers such CD33, HLA-DR, CD14, CD15, CD124 and

programmed death-ligand 1 (PDL1), as well as the intracellular molecule indoleamine 2,3-

dioxygenase (IDO), and were analyzed by flow cytometry using a Fortessa flow cytometer

(Becton Dickinson). M-MDSCs were defined as CD33+ HLADR-/low and CD14+. To

determine the effect of cryopreservation on MDSCs quantification, a subset of samples

were analyzed using both fresh whole PB and isolated PBMCs after a cycle of

freezing/thawing.

Patients displayed higher percentages of m-MDSCs in the PB than healthy controls, as

previously reported. In comparison to healthy controls, patient's m-MDSCs expressed

higher percentages of PD-L1, lower of CD124, and similar proportions of IDO. CD14 and

CD124 expression levels measured by mean fluorescence intensity (MFI) were

upregulated in patient's M-MDSCs. In patients, percentages of m-MDSCs were associated

with parameters of liver damage (fibroscan score and serum ALT levels). Anti-HCV

treatment reduced m-MDSC levels in 3 out of 4 evaluable patients. PBMC isolation and

cryopreservation completely eliminated granulocytic (G)-MDSCs and significantly reduced

the percentages of m-MDSCs, in comparison to fresh whole PB. These results suggest

that PD-L1 could be a therapeutic target in HCV-infected patients in which standard

treatment fails.

www.sci.cat 41

Posters Innate Immunity 16 - 19 The authors will attend the poster on 17/11/2016: 17:30h; 18/11/2016: 11:00h, 13:30h, 16:55h.

18 Beneficial effects of soluble cd6 forms in experimental

polymicrobial sepsis

Mario Martinez Florensa1; Marta Consuegra-Fernández

1; Fernando Aranda Vega

1; Noelia Armiger

1;

María Velasco de Andrés1; Cristina Català Osete

1; Marianna Di Scala

4; Gloria González-

Aseguinolaza4; Francisco Lozano

2,3

1Institut dínvestigaciones biomédicas August Pi i Sunyer IDIBAPS;

2Servei dÍmmunologia, Hospital Clinic

de Barcelona; 3Departament de Biología Cellular, Inmunología y Neurociencies, Facultat de Medicina-UB;

4Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona.

The soluble form of the scavenger-like human CD6 lymphocyte surface receptor (shCD6)

has been shown to bind to pathogen-associated molecular patterns present in Gram-

positive or -negative bacteria, and to be time- and dose-dependent effective when infused

in mouse models of monobacterial-induced sepsis of intraabdominal origin. The aim of the

present work was to demonstrate the efficacy of shCD6 in the prevention and treatment of

polymicrobial sepsis caused by cecal ligation and puncture (CLP). Purified shCD6 protein

was infused either i.p. or i.v. at different doses and time-points prior and after

CLPinduction, alone or in combination with broad-spectrum bactericidal antibiotics

(Imipenem, Meropenem). Significant improvement of mouse survival, reduction in pro-

inflammatory cytokine levels and in bacterial load was observed when shCD6 (1.25 mg/kg)

was infused i.p. at -1h or +1h post-CLP but not beyond. Similar survival rates were

observed when Imipenem (75 mg/Kg/8h) was administered i.p. at the same timepoints.

When shCD6 was infused i.v. significant improvement of mice survival +3h was observed.

Interestingly, additive effects on mouse survival were observed with shCD6 given i.v. in

combination with Imipenem (i.p) both at +1h post-CLP. These beneficial effects were also

observed in mice transduced with AAV expressing the mouse sCD6 equivalent before

CLP-induction. These data support the prophylactic and/or therapeutic use sCD6 from

either human or mouse origin in polymicrobial sepsis, alone or in combination with

bactericidal antibiotics.

Supported by Spanish Ministerio de Economía y Competitividad (SAF2013-46151-R) and

Instituto de Salud Carlos III (Spanish Network for Research in Infectious Diseases,

RD12/0015/0018).

42 www.sci.cat

Posters Innate Immunity 16 - 19


19 Mouse strain differences in the susceptibility to fungal-like

septic shock

Esther Carreras1; María Velasco

1; Inês Simões

1; Marc Orta-Mascaró

1; Francisco Lozano

1,2,3

1Grup d’Immunoreceptors del Sistema Innat i Adaptatiu, Institut d’Investigacions Biomèdiques August Pi i

Sunyer; 2Servei d’Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona;

3Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, Barcelona.

The Zymosan-induced generalized inflammation (ZIGI) is considered an experimental

model of fungal sepsis. First developed in rats, it was also later used mice strains to

investigate possible prophylactic and/or therapeutic interventions. Zymosan is a yeast cell

wall extract mainly composed of ß-glucans and mannans, two conserved fungal pathogen-

associated molecular patterns (PAMPs) that activate complement and are the ligands for

different innate and adaptive immune cell receptors (TLR2, Dectin-1, and CD5), resulting

in a generalized inflammation post-intraperitoneal (i.p.) injection. In this study we compare

the response of inbred C57BL/6 and outbred CD1 mouse strains to ZIGI with the aim of

dissecting immune response factors related to different strain-linked susceptibility to fungal

infection. We found that C57BL/6 mice were more susceptible than CD1 mice to Zymosan

insult. Accordingly, prophylactic i.p. infusion of a soluble form of the human lymphocyte

receptor CD5 (shCD5; 1.25 mg/Kg) –a receptor for fungal β-glucans- significantly

increased CD1 but not C57BL/6 mice survival post-ZIGI. The resistance of CD1 mice to

ZIGI was linked to higher serum levels of the Th1 cytokine interferon (IFN)-γ but not to IL-

17. Consistently, CD1 splenocytes also secreted significantly higher amounts of IFN-γ than

those from C57BL/6 mice when ex vivo exposed to Zymosan. IFN-γ secretion was IL-12-

dependent as blocking anti-IL-12 antibody reduced IFN-γ production ex vivo. The

enhanced ability of CD1 splenocytes to produce IFN-γ was not limited to stimulation by

Zymosan but also to other PAMPS of Gram-negative (Lipopolisaccharide, LPS) or Gram-

positive (Lipoteichoic Acid, LTA) bacterial origin. According to the present in vivo and in

vitro data, IFN-γ (5ng) infusion, either alone or in combination with shCD5 (1.25 mg/Kg), to

C57BL76 mice induced significant increases in mouse survival post-ZIGI. In conclusion,

this report highlights the link between inflammatory response to fungi and genetic

background.

www.sci.cat 43

2017 Events

Lifelong Learning SCI Program 2017

Data i hora: 2 de febrer de 2017, a les 18:30h. “Medicamentos biotecnológicos e inmunogenicidad” Dr. Fernando de Mora Pérez Departamento de Farmacología, de Terapéutica y de Toxicología. UAB. Lloc: Sala 1 Acadèmia de Ciències Mèdiques (Major de Can Caralleu 1-7, Barcelona). Data i hora: 2 de març de 2017, a les 18:30h. “Accion inmunosupresora de las células T reguladoras (CD4+CD25+Foxp3) en la función vascular durante la enfermedad hipertensiva” Dra. María Galán Arroyo (CSIC-ICCC, Barcelona). Lloc: Parc de Recerca Biomèdica de Barcelona (PRBB), sala Xipre 1ª planta (c/Doctor Aiguader 88, Barcelona). Data i hora: 6 d'abril de 2017, a les 18:30h. “Nuclear hormone receptors in chronic inflammatory diseases and the homeostasis of hematopoietic stem cells” Dra. Mercedes Ricote Pacheco (CNIC, Madrid). Lloc: Sales Polivalents, Planta 2, de Hospital de la Santa Creu i Sant Pau (c/ Sant Quintí, 89, Barcelona). Data i hora: 27 d'abril de 2017, dia de la IMMUNOLOGIA, 16h-21h Tema: Inmunoterapias Una iniciativa de la IUIS (International Union of Immunological Societies) amb la col·laboració directa de la EFIS (European Federation of Immunological Societies). Lloc: Institut d’Estudis Catalans, sala Pere i Joan Coromines. c/del Carme 47. Barcelona. Data i hora: 4 de maig de 2017, a les 18:30h. “Immunonutrició en primeres etapes de vida” Dr. Fco. José Pérez Cano (Dept. Fisiologia, UB). Lloc: Hospital Clinic, Sala Farreras Valentí, escales 9-11, (c/Villarroel 170, Barcelona). Data i hora: 1 de juny de 2017, a les 18:30h. “Central T cell tolerance: Identification of tissue-restricted autoantigens in the thymus HLA-DR peptidome” Dra. Dolores Jaraquemada (Dept. Biologia Cel·lular, Fisiologia i Immunologia, UAB, Bellaterra). Lloc: Sala 9, Acadèmia de Ciències Mèdiques (Major de Can Caralleu 1-7, Barcelona). Data i hora: 6 de juliol de 2017, a les 18:30h. “Nous avenços en Esclerosi múltiple” Dr. Xavier Montalban Gairin (CEMCAT, Barcelona). Lloc: Sala 9, Acadèmia de Ciències Mèdiques (Major de Can Caralleu 1-7, Barcelona).

44 www.sci.cat

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List of participants and authors

Abril-Gil M. 35 Agusti A. 23 Alena G. 6 Alvarado-Cardena M. 11 Alvarez de la Sierra D. 27 Amengual M.J. 7 Ampudia R.M. 20, 34 Aranda F. 26, 41 Arias M.T. 26 Armiger-Borràs N. 26, 41 Arpa B. 22 Arufe M.C. 33 Azagra-Boronat I. 6, 16 Balada E. 11 Barquinero J. 40 Baucells de la Peña A. 31 Benítez-Ribas D. 7, 19 Berset C. 18 Bes M. 40 Blanco F.J. 33 Blanco-Cabra N. 15 Borgman K.J.E. 19 Borrego F. 7 Cabezón R. 19 Camps-Bossacoma M. 36 Cano-Sarabia M. 20 Caragol I. 27 Carrascosa J.M. 26 Carreras E. 37, 42 Casacuberta-Serra S. 40 Casademont J. 11 Castell M. 16, 35, 36, 38 Castellví I. 31 Casteras A. 27 Castro-Panete M.J. 14 Català C. 37, 41 Celada A. 21 Centeno C.. 12 Collado J.A. 33 Colobran R. 9, 10 Consuegra-Fernández M. 26, 41 Costa C. 33 Coves E. 40 Crespo M. 13 Cruz T. 7, 23 de Andrés A. 14 de Jesus Gil C. 27 de Jorge-Huerta L. 14 De la Calle O. 5 Di Scala M. 41 Díaz-Ordóñez M. 14 Díez R. 10 Domínguez-Rodríguez S. 14 Egia-Mendikute L. 7, 22

España C. 19 Esteve A. 26 Faner R. 23 Fernandez M.A. 23 Fernández-Pernas P. 33 Ferrándiz C. 26 Ferrer R. 27 Flórez-Grau G. 7, 19 Fonolleda Ramboux M. 30 Franch A. 16, 35, 36, 38 Franco C. 5, 9, 10 Gala G. 9 García E. 9 García L. 10 García M. 10 GarcÍa-Jimeno S. 20 Gehbauer C. 34 Gieras A. 34 Gimeno R. 7 Gonzalez O. 27 González-Aseguinolaza G. 41 Gonzalez-Mera L. 11 Grases-Pintó B. 35, 38 Grau-Junyet, J.M. 11 Guallar-Garrido S. 15 Guarner C. 39 Guilabert A. 26 Hernández C. 32 Hernández Lafuente M.C. 31 Hernández M. 9, 10 Izquierdo C. 20 Juárez C. 2, 5, 6, 7, 11, 25, 31, 32, 39 Julià M. 26 Julián E. 15 Kluge K. 18 Labrador-Horrillo M. 11 Lloberas J. 21 López-Botet M. 13 López-Estévez S. 40 López-Giraldo A. 23 Lozano F. 26, 37, 41, 42 Lucas-Martin A. 27 Luquin M. 15 Mancebo E. 14 Mansilla M.J. 20, 24, 28, 29 Máñez R. 33 Marín A. 5, 11 Mariscal-Rodríguez A. 31, 32 Marquina M. 33 Martín A. 9, 10 Martínez M. 41 Martínez M.A. 11 Martínez-Acebes E. 11 Martínez-Cáceres E.M. 12, 20, 24, 28, 29, 30

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Martínez-Florensa M. 26, 37 Martínez-Martínez L. 11, 31, 32 Martos S. 9 Mas V. 5 Mascaró-Galy J.M. 26 Maspoch D 20 Massot-Cladera M. 16 Mediano C. 10 Mestre J. 9 Moga E. 25 Moltó Lacosta E. 31 Mora C. 22 Morales J.M. 14 Moreno P.J. 11 Moriarty F. 18 Mundet-Tuduri X. 11 Muntasell A. 13 Muñoz C. 26 Navarro-Barriuso J. 20, 28, 29 Nieto J.C. 39 Noell G. 23 Noguera-Ortega E. 6, 15 Obiols G. 27 Olive A. 12 O'Mahony L. 18 Orta-Mascaró M. 42 Parés M. 40 Pascual J. 13 Paz-Artal E. 14 Pedrosa E. 26 Perea L. 39 Pereira-Lopes S. 21 Pérez-Cano F.J. 6, 16, 35, 36, 38 Pérez-Cruz M. 33 Pérez-Fernández S. 13 Pérez-Sáez M.J. 13 Perna-Barrull D. 20, 34 Pich C. 17 Pinal-Fernandez I. 11 Plaja A. 10 Poca M. 39 Portillo K. 12 Presas S. 28, 29 Puig L. 25 Pujol-Autonell I. 20, 34 Pujol-Borrell R. 9, 11, 27 Pule M. 5 Querol L. 31, 32 Quirant-Sánchez B. 12, 24, 28, 29, 30 Rabanal R.M. 15 Ramo-Tello C. 24, 28, 29 Redondo-Pachón D. 5, 13 Richards G. 18 Rius-Rigau A. 28, 29

Rodriguez-Fernandez S. 7, 20, 34 Rodríguez-Lagunas M.J. 16, 35, 38 Roldán M. 15 Román E. 39 Romaní J. 26 Romero C. 39 Rosell-Mases E. 22 Rudilla F. 6 Ruiz-Martínez L. 14 Rus A. 12 Sabaté M. 6, 18 Salvador I. 5, 12 Sánchez A. 28, 29 Sánchez E. 39 Sánchez M. 25 Sánchez-Chardi A. 15 Sánchez-Zapardiel E. 6, 14 Santiago F. 26 Santos C. 22 Sanz M.T. 25 Sarrabayrouse G. 6, 17 Sauleda S. 40 Selva A. 11 Serracant-Prat A. 34 Serrano A. 14 Serreze D. 22 Simões I. 37, 42 Sirera R. 5 Soler P. 9, 10 Soriano A. 12 Soriano G. 39 Soriano Martínez A 30 Stratmann T. 20, 22 Teiti I. 17 Teniente-Serra A. 12, 24, 28, 29, 30 Tilkin-Mariame A.F. 17 Tolosa E. 34 Torrents E. 15 Torres-Castro P. 38 Trevijano-Contador N. 37 Tur J. 7, 21 Utrero-Rico A. 14 Valledor A. 5, 6 Van Ginderachter J. 6 Velasco de Andrés M. 37, 41, 42 Verdaguer J. 20, 22 Vicente Hervás J. 24 Vidal S. 25, 39 Vila J. 13 Vilches C. 13 Vived C. 22 Vives-Pi M. 20, 22, 34 Yélamos J. 13 Zaragoza O. 37

48 www.sci.cat

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X CONGRÉS

Societat Catalana d’Immunologia (SCI)

Barcelona, 17 i 18 de novembre 2016

The contents of this congress will be accessible in few months in our website www.congressci.com

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X CONGRÉS...described (Franco-Jarava et al. J Clin Immunol 2016; 36:388-96) that standard capillary protein electrophoresis can be used to detect sera which may have low C3 levels