Pathogenicity of mixed cryoglobulin formation
Steps involved in mixed cryoglobulin formation and their pathogenicity
This process has been most extensively studied in HCV-associated MC. Expansion of B lymphocytes is the hallmark and is thought to result from chronic immune stimulation. HCV has a membrane protein, E2, that binds to CD81 on B cells and is thought to be directly involved in B-cell stimulation. These cells produce Igs with RF activity, especially a particular variant designated the WA cross-idiotype. Complexes of HCV components, Igs, RF, complement, and other particles (e.g., very low-density lipoprotein) comprise the cryoglobulin. Cryoglobulins may persist despite viral clearance following treatment (and may no longer contain viral particles), suggesting that cryoglobulin formation may initially be a virus-dependent phenomenon that eventually becomes autonomous. Tissue deposition, complement fixation, and the following inflammatory cascade result in vasculitis. The fact that a particular B-cell activating factor (BAFF) promoter polymorphism and elevated levels of BAFF are found in patients with MC suggests that it may have a pathogenic role by promoting B-cell proliferation and survival.
