Cryoprecipitate of patients with cryoglobulinemic glomerulonephritis contains molecules of the lectin complement pathway

Serological and histological studies were carried out to explore the role o f the lectin complement pathway in the pathogenesis of cryoglobulinemic glo merulonephritis. Sixteen patients with mixed cryoglobulinemia type II with glomerulonephritis (GN) were enrolled. All cases had hepatitis C virus (HCV ) infection. The serum concentration of mannose-binding lectin (MBL) was si gnificantly higher in the GN patients than in the normal controls according to ELISA (P<0.01). IgG, IgM, C1q, C4d, HCV envelope antigen, MBL, and MBL- associated serine protease-1 (MASP-1) could be visualized in the cryoprecip itate of the 16 patients by Dot blot assay. Renal biopsy specimens obtained from 3 patients were examined by immunohistochemistry, and the glomeruli s trongly stained for IgG, IgM, MBL, MASP-1, C4d, C3c, and C3d in a fringe-li ke pattern. The pattern of HCV constituent deposition was partially fringe- like. The complement profiles of the 16 cases were distinctive; briefly, th e serum levels of C1q, C2, and C3 were reduced, although the levels of circ ulating regulatory proteins (C1-inhibitor, factor, H, and factor I) were in the normal range. The serum C4 level was significantly reduced. These resu lts indicate that immune complex formation involves molecules of the lectin pathway and leads to organ damage in cryoglobulinemic glomerulonephritis. (C) 2001 Academic Press.