Glomerular deposition of mannose-binding lectin in human glomerulonephritis

Background. Mannose-binding lectin (MBL), a member of the collectin family, binds to various oligosaccharides and activates the classical pathway of c omplement independent from Clq. At present it is unknown whether this so-ca lled lectin pathway of complement activation plays a role in the pathogenes is of human glomerulonephritis. Methods, Direct immunofluorescence of 84 renal biopsies using an MEL-specif ic monoclonal antibody and antibodies directed against IgG, IgA, IgM, Clq, C3, and terminal complement complex (TCC) was performed. Serum MBL levels o f 50 patients were determined by enzyme-linked immunosorbent assay. Results. MBL was detected in the glomeruli of patients with lupus nephropat hy(15 of 16), membranous nephropathy (10/15), membranoproliferative glomeru lonephritis type I (5/6) and anti-GEM nephritis (2/4). MBL deposition paral leled that of immunoglobulins, Clq, C3, and TCC but was less intense as com pared to Clq. Focal segmental deposits of MBL were present in focal segment al glomerulosclerosis (4/6), IgA nephopathy (3/11), amyloidosis AL (1/4), a nd advanced renal fibrosis (2/2). Here MBL staining was identical to IgM an d C3 and considered an unspecific entrapment of MBL in sclerotic lesions in these cases. No significant difference in MBL serum levels was observed be tween normal controls and patients with lupus nephritis, membranous nephrop athy, membranoproliferative glomerulonephritis, focal segmental sclerosis, minimal change disease or IgA nephropathy. In patients suffering from membr anous nephropathy with (n = 10) or without (n = 5) glomerular MBL deposits serum creatinine, C3, C4, serum protein, and proteinuria were not statistic ally different. Conclusion. MBL is present in the glomeruli of patients with glomerulonephr itis involving deposition of IgG and activation of the classical pathway of complement. We propose that MBL binds to agalacto-syl oligosaccarides of I gG that terminate in N-acetylglucosamine. The extent to which the lectin pa thway of complement contributes to overall complement activation in the glo meruli remains unknown, but is likely to be marginal.