The B lymphocyte stimulator receptor-ligand system in hepatitis C virus-induced B cell clonal disorders

Objective: The study aim was to examine the B lymphocyte stimulator ( BLyS) receptor-ligand system in hepatitis C virus (HCV)-induced B lymphocyte clonal disorders. Methods: 94 patients with chronic HCV ( including 35 with HCV+ mixed cryoglobulinaemia (MC)-vasculitis and nine with HCV+ B cell non-Hodgkin's lymphoma (B-NHL)) and 15 healthy volunteers were included. Results: A twofold serum BLyS increase was associated with HCV-induced MC-vasculitis, and a threefold increase with HCV-induced B-NHL, compared with patients that were HCV+, but without vasculitis, or healthy controls (p < 0.05). Lower membrane BLyS expression in HCV-induced MC-vasculitis was observed. CD19+ BLyS binding and BLyS receptor 3 (BR3) staining showed a stepwise decrease with highest values in healthy controls and who were HCV+ without MC, and lowest in B-NHL (p < 0.05, p < 0.0001, respectively) with a further decrease in V(H)1-69+ clonal B cells. BLyS anti-apoptotic effects were maintained despite this decrease in BR3 staining. Complete clinical remission after antiviral treatment was associated with a decrease in serum BLyS, and an increase in BR3 staining. Rituximab treatment was associated with a fivefold increase in serum BLyS (p < 0.001), mirroring the depletion of CD19+ cells. BR3 staining in repopulating B cells was significantly decreased (p < 0.005). Conclusions: The BLyS ligand-receptor activity is increased in HCV-induced B cell clonal disorders, indicating a possible role for treatment targeting the BLyS receptor-ligand system.