Abstract
Pemphigus vulgaris (PV) is a severe autoimmune disease affecting the skin and mucous membranes, characterized by autoantibodies mainly against desmoglein 3 (dsg3). This study investigated the effects of different treatment options on two B-cell mediators, B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), in 19 PV patients on immunosuppressive drugs alone or in combination with immunoadsorption and anti-CD20 antibody, respectively. Serum BAFF and APRIL levels, circulating desmoglein-reactive autoantibodies, and serum IgG specific for varicella-zoster virus (VZV) and Epstein-Barr virus (EBV) were determined by ELISA before and at different time points after initiation of the respective therapy. In contrast to immunosuppressive therapy alone and in combination with adjuvant immunoadsorption, respectively, rituximab treatment led to a strong and significant elevation of BAFF, but not of APRIL levels, which normalized upon recovery of peripheral CD19(+) B cells. Moreover, rituximab treatment led to a statistically significant increase of anti-VZV-IgG and anti-EBV-IgG titers, whereas anti-dsg1 and -3 specific autoantibody titers decreased significantly. Our results suggest that elevated BAFF levels might exert a differential effect on the induction of autoreactive versus pathogen-specific IgG antibody production in PV patients, possibly due to promotion of antibody release of pathogen-specific long-lived plasma cells.