J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 2

Abstracts AB69

SATURDAY

245 Diagnostic Immunization With Bacteriophage UX 174 In

Patients With Common Variable Immunodeficiency/Hypogammaglobulinemia

Dr. Lauren Smith, MD1, Dr. Rebecca H. Buckley, MD, FAAAAI1,

Dr. Patricia L. Lugar, MD, MS2; 1Department of Pediatrics, Duke Univer-

sity Medical Center, Durham, NC, 2Duke University Medical Center,

Durham, NC.

RATIONALE: The use of the T cell-dependent neoantigen bacteriophage

FX 174 has been described since the 1960s as a method to assess specific

antibody response in patients with primary immune deficiencies. We

reviewed a cohort of patients at Duke University Medical Center (DUMC)

who received immunization with bacteriophage and report the clinical

utility and safety of the immunization, as well as patient characteristics.

METHODS: A retrospective chart review was performed of all Duke

Immunology Clinic patients (pediatric and adult) who received immuni-

zation with bacteriophage, from 1976-2012. Subjects were selected for

inclusion if their diagnosis at the time of bacteriophage was either

presumed or confirmed common variable immunodeficiency (CVID),

hypogammaglobulinemia, transient hypogammaglobulinemia, or antibody

deficiency unspecified. Follow up post-immunization was also recorded.

RESULTS: One hundred nineteen patients were identified, 29 adult and 90

pediatric patients. Diagnoses prior to bacteriophage were CVID (n593),

hypogammaglobulinemia (n523), and antibody deficiency (n53). Post-

immunization diagnoses were CVID (n563), hypogammaglobulinemia

(n516), unknown (n525), normal patient (n58), and other primary

immune deficiency (n57). Seventy-four patients had abnormal bacterio-

phage results, 31 were normal, and 14 were borderline. There were 257

recorded administrations of the immunization. Data on reactions was

recorded for 205 immunizations. Fourteen immunizations were associated

with minor adverse events. Seventeen patients stopped their immune

globulin replacement therapy based on reported immunization response.

CONCLUSIONS: Bacteriophage FX 174 is a clinically useful and safe

method to assess antibody response in patients with suspected antibody-

mediated immune deficiencies, particularly those who are on immune

globulin replacement therapy at the time of immunization.

246 Immunochip Study Reveals Regions On Chromosomes 2 and 6May Contribute To The Spectrum Of CVID

Dr. Tracy Hwangpo, MD/PhD1, Ewa Szymanksa, PhD1, Mrs. Marsha

Brand1, Dr. Peter Gregerson, MD2, Dr. Peter Burrows, PhD3,

Dr. Elizabeth Brown, PhD4, Dr. Richard Reynolds, PhD5, Dr. Harry

Schroeder, MD/PhD6; 1UAB, 2The Feinstein Institute for Medical

Research, 3UAB, Department of Microbiology, 4UAB, Department of

Epidemiology, 5UAB, Department of Medicine, 6UAB, Department of

Medicine and Department of Microbiology, AL.

RATIONALE: In our PID Clinic, we have cared for more than 300

patients with recurrent infections and depressed immunoglobulins. We

have enrolled a majority of them in a protocol to identify regions within the

genome that may contribute to the spectrum of their disease. We are

interested in patients with CVID as well as a spectrum of patients who do

not meet CVID criteria.

METHODS: We included a total of 1,422 cases and controls of European

American ancestry; of which, 81 were diagnosed with CVID, 84 with

intermediate CVID (ICR), and 75 with RESPI. Relative risk was estimated

using odds ratios and corresponding 95% confidence intervals as

implemented in PLINK using log-additive models and linkage disequilib-

rium was assessed using Haploview and LocusZoom.

RESULTS: The strongest gene associations with CVID were mapped to

several loci on chromosomes 2 and 6. Specifically, on chromosome 2, loci

mapped to the genes that encode endonuclease ZRANB3 and the GTPase

activating protein RAB3GAP1 were strongly associated with CVID

compared to controls (p56.00X10-12 and 6.59x10-12, respectively). On

chromosome 6, rs2523535, localized to HLA-B, was associated with

CVID (p53.13x10-9). When we expanded our analysis to include all

phenotypes consistent with the spectrum of disease, similar regions on

chromosomes 2 and 6 were also strongly associated.

CONCLUSIONS: This study exposes new and unexplored regions of

interest within chromosomes 2 and 6 in the CVID population. Further study

of these areas may show new gene(s) that may contribute to the disease.

247 Rule Of Different Memory Cells In Common VariableImmunodeficiency and Specific Antibody Deficiency

Amer M. Khojah, MD1, Oral Alpan, MD2, Ameera Bukhari, MS3;1Umm Al Qura Univirsity, Makkah, Saudi Arabia; Inova Fairfax Hospital

for children, Fall Church, VA, 2Amerimmune, LLC, VA; O&O ALPAN,

LLC, 3Taif University, Saudi Arabia.

RATIONALE: SAD diagnosis relies on abnormal response to pneumo-

coccal vaccine. The purpose of our study is finding a flow cytometry

marker for early detection of SAD.

METHODS: Total of 361 subjects (205 adults and 156 children) were

included in study between 2010 and 2013. Patients with known immuno-

deficiency other than SAD and CVID were excluded. Subjects were

divided into 3 groups (control, SAD, CVID) based on their immunoglob-

ulin levels and their response to pneumococcal vaccines. Data was

analyzed using SPSS.

RESULTS: We found that SAD and CVID have significant lower number

of memory B-cell. Furthermore, we found that percentage of memory B-

cell increases with age in control group (correlation coefficient5 0.4, P

value 0.0001) but not CVID or SAD groups. However, Memory T-helper

cell increaseswith age in all three groups (correlation coefficient 0.71-0.78,

P value 0.0001).There was direct correlation between memory B-cell and

CD4+ memory T-cell (correlation coefficient 0.39 with P value <0.0001),

and this correlation was inversed in SAD (correlation coefficient -0.45 with

P value of 0.007). Using CD4+ memory T-cell to memory B-cell ratio of

4.5 as a marker for SAD had specificity of 98% but poor sensitivity of 31%.

CONCLUSIONS: Our findings suggest that there is impaired correlation,

either developmentally or acquired through negative feedback, between

CD4+ memory T-cell and memory B-cell in SAD patients. Using the ratio

of CD4+memory T-cell to memory B-cell helps identifying distinct cluster

of SAD patients and future research is need to evaluate its prognostic value.