Mixed cryoglobulinemia (MC) cross-reactive idiotypes (CRI): Structural and clinical significance

Abstract

A review of mixed cryoglobulinemia (MC) cross-reactive idiotypes (CRI) published 20 years ago (Sem Hematol 28, 79-94, 1991) is updated to include information regarding the structural correlates of these CRIs, prevalence and expression on specific B-cell subsets in hepatitis C virus (HCV) infection, and the occurrence of lymphoproliferative diseases complicating MC, HCV, and primary Sjögren's syndrome (SS). MC occurring in association with HCV or primary SS shares selective usage of specific V-region H-chain (V1-69; V3-7; V4-59) and/or κ L-chain (V3-20; V3-15) genes, expression of which has been correlated with polyclonal (Wa) or monoclonal (Ccl-1; Lcl-1; G6; G8; 17.109) antibodies to MC CRIs expressed on CD27+ memory B cells in the peripheral blood of patients productively infected by HCV. In HCV, the expression of MC CRIs recognized by monoclonal and polyclonal antibodies to these idiotypes may be expanded on specific B-cell subsets or may provide a marker for coexistent lymphoproliferative disease, both of which may regress with clearance of the virus. In other instances, MC CRI and cryoglobulinemia may persist even after successful antiviral therapy. The full utility of antibodies to MC CRIs for diagnosis and treatment remains to be defined.