Evaluation of the B Cell Compartment in CVID and Respi Patients

Abstract

S D A Y 819 Evaluation of the B Cell Compartment in CVID and Respi Patients Tracy Hwangpo, MD, PhD, Ewa Szymanksa, Cunren Liu, Marsha Brand, Elizabeth Brown, Harry Schroeder; UAB, UAB, AL. RATIONALE: Recent studies suggest that clinical symptoms in CVID can correlate with a reduction in the memory B cell compartment. We are characterizing various B cell populations of patients without disease, with CVID, and with REcurrent Sino-Pulmonary Infections and normal serum immunoglobulins (RESPI) as an effort to find distinguishing features among them. METHODS: Whole blood was collected from over 140 study subjects. Total lymphocytes, marginal zone-like B cells, IgM+ memory B cells, class-switched B cells, transitional B cells, immature B cells, and na€ive B cells were isolated and evaluated by flow cytometry. Immunoglobulins and HLA haplotyewere also examined. Unpaired t-test was used to analyze the means of these cells. RESULTS:We found that by disease phenotype, RESPI patients appear to have lower IgG levels compared to control patients. All B cell subsets were decreased in CVID patients, particularly classed-switchedmemory B cells. There is a gradient for marginal zone-like B cells, with CVID having the lowest numbers compared to RESPI and controls. IgM+ memory B cells were found to be lower in RESPI patients compared to controls. We also found patients with the B4/B88 haplotype tended to have lower B cell subsets. Analysis is ongoing for transitional, naive, and immature B cells. CONCLUSIONS: We postulate that the transition fromRESPI patients to CVID patientsmay involve the development of defects in B cell maturation signaling or memory B cell generation. We identified the distinctive features of lower IgM memory B cells in RESPI patients compared to controls. Characterizing the B cell compartment may elucidate their importance in disease identification and progression.