Altered dendritic cell distribution in patients with common variable immunodeficiency

Abstract

Recent data suggest a critical role for dendritic cells (DCs) in the generation of immunoglobulin-secreting plasma cells. In the work reported herein, we analyzed the frequency of peripheral blood plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in a cohort of 44 adults with common variable immunodeficiency (CVID) classified according to their CD27 membrane expression status on B cells. A deep alteration in the distribution of DC subsets, especially of pDCs, in the peripheral blood of CVID patients was found. Patients with a reduced number of class-switched CD27+IgD-IgM- memory B cells and patients with granulomatous disease had a dramatic decrease in pDCs (P = 0.00005 and 0.0003 vs controls, respectively) and, to a lesser extent, of mDCs (P = 0.001 and 0.01 vs controls, respectively). In contrast, patients with normal numbers of switched memory B cells had a DC distribution pattern similar to that in controls. Taken together, our results raise the possibility that innate immunity contributes to pathogenesis in CVID.

Figure 1

Absolute counts of pDCs and mDCs in 45 CVID patients and 12 controls. Medians of absolute counts of peripheral blood lymphoid dendritic cells (pDCs) (white boxes; □∘) and myeloid DCs (shaded boxes; Δ) in 12 control subjects (respective median values, 9,829/ml and 14,361/ml; extreme values, 7,514 to 22,769/ml and 8,941 to 22,204/ml) and 44 patients with common variable immunodeficiency (CVID) (respective median values, 3,647/ml and 11,100/ml; extreme values, 19 to 22,144/ml and 342 to 28,472/ml). The symbol within each box represents the median value. The upper and lower edges of the boxes represent the 25th and 75th percentiles, and the bars on the whiskers represent the 10th and 90th percentiles. s represents an aberrant value. Statistical comparisons between the two populations (nonparametric Mann–Whitney U test): P = 0.002 for pDCs and P = 0.1 for mDCs.