Mesangial deposition of IgA2 subclass and lectin pathway‐mediated complement activation in IgA glomerulonephritis

Three pathways are recognized in the complement activation cascade. The aim of our study was to elucidate immunohistologically which complement pathway is associated with the activation in IgA glomerulonephritis (GN) and the relation of IgA subclass to the complement activation. Immunohistological staining was performed on biopsied renal specimens from 36 patients with IgA GN, 10 with systemic lupus erythematosus (SLE) and 16 with other glomerulonephritides using polyclonal antibodies of IgG, IgA, IgM, C3c, C4, C1q and monoclonal antibodies of IgA1, IgA2, mannose‐binding lectin (MBL) and MBL‐associated serine protease‐1 (MASP‐1). Mesangial deposits of IgA1, IgA2, C3c, C4, MBL and MASP‐1 were detected in 19 of the 36 patients with IgA GN, and IgA2 and MBL/MASP‐1 were colocalized in the mesangium in these 19 patients. The remaining 17 patients showed mesangial deposition of IgA1 alone. Twelve of these 17 patients presented mesangial deposition of C3c without deposition of C4, MBL and MASP‐1. No deposition of C1q was evident in IgA GN patients. Three of the 10 SLE patients showed glomerular deposition of MBL and MASP‐1 without deposition of IgA2. No patient with other glomerulonephritides showed glomerular deposition of IgA1, IgA2, MBL and MASP‐1. There was no correlation in clinical and pathological indicators between IgA2‐positive and IgA2‐negative patients with IgA GN. In conclusion, alternative pathway‐mediated complement activation is associated in patients with mesangial deposition of IgA1 alone in IgA GN. In those with the deposition of both IgA1 and IgA2, both alternative and lectin pathways are activated, and mesangial deposition of IgA2 is associated with the lectin pathway‐mediated complement activation in IgA GN.