Phenotypic comparison of B cells in discordant identical twins with common variable immunodeficiency and recurrent sino-pulmonary infection patients

RATIONALE: In our Adult Primary Immunodeficiency Clinic in the Southeastern United States, we observed that nearly half of our patients with Common Variable Immune Deficiency (CVID) and half of our patients with recurrent sinopulmonary infections with normal serum immunoglobulins (RESPI) inherit HLA∗B44. Recent studies by others suggest that clinical symptoms in CVID can correlate with a reduction in the memory B cell compartment. To test this hypothesis, we evaluated serial B cell numbers over time in a set of identical HLA∗B44+ twins discordant for CVID and RESPI. METHODS: Whole blood was collected at a minimum of seven time points over a 14 month period. Plasma cells, memory B cells, immature B cells, transitional B cells, and mature B cells were isolated from whole blood and counted via FACS. One-way ANOVA and 2-sample test were used to analyze the means of these cells. RESULTS: Memory IgD+ and memory IgD- cells were significantly lower in the CVID twin (mean 3.2X105 in CVID, 1.0X106 in RESPI, p <0.012; mean 2.4X105 in CVID, 8.2X105 in RESPI, p <0.017, respectively). There was a trend for higher immature B cells and lower transitional B cells in the CVID twin compared to the RESPI twin although this did not reach statistical significance. CONCLUSIONS: The twin with CVID appears to have fewer memory B cells, fewer transitional cells, and more immature B cells than her RESPI twin sister. Defects in either B cell maturation signaling or memory B cell generation may be contributing to the discordant phenotype.