Mesangial IgA2 deposits and lectin pathway-mediated complement activation in IgA glomerulonephritis

Three pathways are recognized in complement activation. The aim of our stud y is to elucidate immunohistologically which complement pathway is associat ed with complement activation in immunoglobulin A (IgA) glomerulonephritis (GN) and which IgA subclass is related to complement activation. Immunohist ological staining was performed on renal biopsy specimens obtained from 36 patients with IgA GN, 10 patients with systemic lupus erythematosus (SLE), and 16 patients with other GNs using polyclonal antibodies of IgG, IgA, IgM , G1q, C3c, andC4 and monoclonal antibodies of IgA1, IgA2, mannose-binding lectin (MBL), and MBL-associated serine protease-1 (MASP-1). Mesangial depo sits of both IgA1 and IgA2 were found in 19 of 36 patients with IgA GN. Mes angial deposits of C3c, C4, MBL, and MASP-1 also were detected in these 19 patients, and IgA2, MBL, and MASP-1 deposits were colocalized in the mesang ium in these patients. The remaining 17 patients showed mesangial deposits of IgA1 alone. Twelve of these 17 patients showed mesangial deposits of C3c without C4, MBL, or MASP-1. No deposition of Clq Was evident in patients w ith IgA GN. Three of 10 patients with SLE showed glomerular deposition of M BL and MASP-1 without glomerular deposition of IgA2. None of the Patients w ith other GNs showed glomerular deposition of IgA1, IgA2, MBL, or MASP-1. T here was no correlation in clinical or pathological indicators between IgA2 -positive and IgA2-negative patients with IgA GN. In conclusion, alternativ e pathway-involved complement activation is associated with mesangial depos its. of IgA1 alone in patients with IgA GN. In those with mesangial deposit s of both IgA1 and IgA2, both the alternative and lectin pathways are invol ved in complement activation. We first report that mesangial deposits of Ig A2 may activate the lectin pathway in patients with IgA GN. (C) 2001 by the National Kidney Foundation, Inc.