Relationship of tissue deposits of cryoglobulin to clinical features of mixed cryoglobulinemia.

Two patients with type 2 mixed cryoglobulinemia had tissue deposits of serum cryoproteins. Patient 1, a 72-year-old man, had purpura and glomerulonephritis. The serum cryoglobulin consisted of monoclonal IgM kappa and polyclonal IgG. Renal biopsy revealed diffuse proliferative glomerulonephritis with abundant IgG, IgM, kappa light chain, and complement in glomerular capillary walls. These immunoglobulins, but no complement, were also present in histologically normal cutaneous blood vessels. Ultrastructurally, cutaneous vascular deposits were identical to the renal deposits and to the crystalline mixed IgM-IgG serum cryoprecipitates and renal deposits previously described. Patient 2 was a 68-year-old man with sensorimotor peripheral polyneuropathy and purpura. His serum cryoglobulin consisted of monoclonal IgA lambda and polyclonal IgG. Sural nerve and skin biopsies revealed vasculitis involving small arteries and arterioles. Immunoglobulin A and complement were present in perineurial arteriolar walls of the sural nerve. Cryoprecipitates in both cases had strong rheumatoid factor activity. These findings support the view that in type 2 cryoglobulinemia tissue deposits consist of cryoprotein immune complexes. The presence of these deposits in histologically normal blood vessels in patient 1 suggests that deposition of cryoproteins precedes and may initiate tissue damage.