Switched memory B cells in common variable immunodeficiency

Abstract

Rationale We have examined in vivo laboratory values of common variable immunodeficiency (CVID) patients in order to validate the classification scheme of Warnatz (Blood 2002;99:1544-1551, based on populations of switched memory (CD27+) B cells). Methods 33 subjects with CVID were studied. Percentage of switched memory B-cells (CD27+IgM-IgD-) were calculated using flow cytometry; patients were subdivided into group I (<0.4% CD27+IgM-IgD-/peripheral lymphocytes) and group II (>0.4%). Serum immunoglobulins and post-pneumococcal vaccine response were compared for the two groups. Results Tested patients were age 3 to 77. 17 patients (52%) were placed in group I (CD27+IgM-IgD- mean=0.17 ± 0.11, range=0.04-0.38) and 16 (48%) in group II (CD27+IgM-IgD- mean=1.42 ± 1.48, range=0.41-6.5,). Mean age was 43.4 ± 20.0 in group I and 43.4 ± 15.6 in group II. Mean IgG (Igs in mg/dl) was 213.6 ± 162.0 (range=13-527) in group I and 325.9 ± 184.4 in group II (range=33-604) with P-value=0.074 by paired t-test. Mean IgA was 13.7 ± 14.1 vs. 39.5 ± 21.0, but P=0.16. The mean IgM (34.9 ± 31.8 vs. 39.5 ± 36.4, P=0.71) was similar. Post-pneumococcal vaccine titers were tested in 9 group I and 10 group II patients. Mean protective response (serotypes out of 12) was 1.78 ± 3.35 vs. 4.50 ± 4.30 (but P=0.14). Conclusion Patients with higher numbers of switched memory B-cells have non statistically significant higher levels of serum IgG, IgA, and IgM and improved response to pneumococcal vaccine than patients with lower numbers of these cells. While there is still significant heterogeneity within each group, these results suggest that subdividing CVID patients by switched memory B-cells might be useful in conjunction with other measures to classify patients for genetic and functional analysis.