SERUM CYTOKINE PATTERNS IN CELIAC

DISEASEShabab Naqvi & Ibrahim Ibrahim

Mentor: Dr. Sanil Manavalan

Columbia University, College of Physicians and Surgeons

Celiac disease

•a digestive disease that damages the small intestine and interferes with absorption of nutrients from food•it is a genetic disorder•some of the symptoms of celiac disease are diarrhea, weight loss, malnutrition, etc•when people with celiac disease eat foods containing gluten, their immune system responds by damaging the small intestine•Diagnosis is by intestinal biopsy histological grading and presence of serum auto- antibodies.

Key Terms• Cytokines – soluble peptides or glycoproteins that regulate

immune, inflammatory responses and other biologic processes. – Interleukin (IL) – cytokines that only affect leukocytes.

• Lymphocyte – A type of leukocyte (white blood cell) of the immune system.– T-Regulatory Cell – slows down and stops immune

response– T-Helper Cell (Th cell) – has antigen-receptors, releases

cytokines– Natural Killer Cell – kills macrophage and bad stuff– Cytotoxic T-Cell – kills cells that produce foreign antigens

such as cells infected by viruses– B-Cell – creates antibodies.

• Antigen – invading microbe

• Antibody – protein that fights bacteria and viruses.

The Gut LumenThe Gut Lumen

Gliadin

Enterocytes

GUT LUMEN

Antibodiesanti-gliadin

anti-endomysialAnd tissue trasgliutaminase

Cytokines(Interferon-, TNF-IL-15 etc)

Lymphocytes(T cells , Natural Killer cells and B cells)

Plasma cells

T cell receptor

Helper T cell

HLA-DQ2/DQ8molecule

Antigen Presenting Cell

GUT LUMEN

LAMINA PROPRIA AND INTRA EPITHILIAL SPACE

Inflammation &Damaged

enterocytes

Define the serum cytokine profile in patients with Celiac Disease:

AIMS

A) Active Disease B) Gluten Free Diet (GFD) C) Refractory disease (RD) D) Normals/Controls

APC DerivedIL-8, IL-1, IL-1,

TNF-

Th-1 Derived

IL-2IFN-γ

Cytokines Measured:

Th-2 Derived

IL-4IL-6IL-10

METHODOLOGYSerum Samples from:

A) Active Disease (25) B) Gluten Free Diet (GFD) (43) C) Refractory disease (6) D) Controls (16)

Measured using a Cytokine Bio-chip Array (RANDOX laboratories Ltd)

Mann-Whitney Rank test and Student T-test to determine differences in the means of individual groups of patients:

0

20

40

60

80

100

0

10

20

30

40

50

P = 0.01

P <0.005 P = 0.004

P = 0.006 P = 0.06

P = 0.04

GFDActives RefractoryNormal

Normal

Actives GFD Refractory

IFN-

(p

g/m

l)

IL-4

(pg/

ml)

RESULTS

IFN- IL-4

ACTIVE CD VS. NORMALS

IL-4 P <0.004

IL-6 P <0.008

IL-10 P < 0.01

IL-2 P < 0.04

IFN- P < 0.005

IL-1 P = 0.13

IL-1 P = 0.38

IL-8 P<0.0007

TNF-α P <0.03

APC Derived

Th-2 DerivedTh-1 Derived

Active CD n= 25Controls n= 16

GFD vs. Normals

IL-4 P <0.0006

IL-6 P <0.015

IL-10 P = 0.13

IL-2 P = 0.09

IFN-

P < 0.01

IL-1 P = 0.42

IL-1 P = 0.87

IL-8 P <0.003

TNF-α P = 0.09

APC Derived

Th-2 DerivedTh-1 Derived

GFD n= 43Controls n=16

SUMMARY

• Patients with Celiac Disease (AD, GFD or RD) have significantly higher levels of pro-inflammatory, TH1( (IFN-γ) and TH2 (IL-4, IL-6, IL-8) cytokines when compared to normal controls.

• Patients on therapy (gluten-free-diet) had fewer pro-inflammatory cytokines with elevated levels than Active disease patients

CONCLUSIONSA better understanding of cytokine

abnormalities may provide insight into: -Systemic symptoms -Disease pathogenesis -Better monitoring of disease activity -New therapeutic and prognostic modalities

THANK YOU

To: Dr. Sanil ManavalanDr. Jamal Naiyer

Dr. Sat BhattacharyaHarlem Children Society