Up-regulation of b-lymphocyte stimulator (BLyS) in patients with mixed cryoglobulinemia

Abstract

The B-lymphocyte stimulator BLyS is one of the key regulators of B cell survival and proliferation. Consistent with this function, high BLyS levels in the serum and/or in affected tissues have been documented in several autoimmune and lymphoproliferative diseases. In patients with mixed cryoglobulinemic syndrome (MCsn), BLyS serum levels are significantly elevated and correlate with markers of HCV-associated B-cell lymphoproliferation. BlyS is also increased, however, in HCV-infected individuals without MCsn. Thus, HCV infection appears to be a crucial, early trigger of BLyS up-regulation. BLyS expression induced by HCV infection or by other pathogenetic events may therefore favor the development of autoimmune and lymphoproliferative features. While the etiologic role of chronic infection is well established in MCsn, such information is lacking in other autoimmune diseases, in which the role of a putative infectious trigger is strongly hypothesized. Accordingly, BLyS up-regulation in HCV-positive MC is an important model linking viral infection, B cell proliferation, and autoimmune disease. Besides direct targeting of the infectious trigger HCV and the B-cell autoimmune/lymphoproliferative disorder, indirect B-cell targeting might likewise prove effective in the treatment of HCV-related MCsn.