The pathogenetic significance of C5b-9 in IgA nephropathy

Renal biopsies from 20 patients with IgAN were retrospectively studied using monoclonal antibodies against T cells, monocytes/macrophages (MM), HLA-DR-related antigen and the C5b-9 neoantigen. Glomerular C5b-9 deposits were mainly found in the mesangial areas and showed an association with IgA (P < 0.005) and C3 deposits (P < 0.001). Interstitial T cells and MM were highly correlated with the interstitial DR + ve cells (P < 0.001 and P < 0.0005 respectively). Tubular C5b-9 deposition was observed on the tubular basement membranes and related to the numbers of interstitial T cells (P < 0.005), MM (P < 0.005) and DR + ve cells (P < 0.01) as well as to the tubular DR expression (P < 0.025). The severity of tubular atrophy and interstitial fibrosis showed a positive correlation with the interstitial T cells, MM and DR + ve cells, as well as with the intensity of tubular C5b-9 deposition (P < 0.05 and P < 0.05 respectively). Plasma creatinine on presentation was correlated with the numbers of interstitial T cells (P < 0.05), MM (P < 0.01), interstitial DR + ve cells (P < 0.005), and tubular C5b-9 deposits (P < 0.005). No correlation between glomerular T cells, MM, and C5b-9 deposits with plasma creatinine was seen. During follow-up, renal function deteriorated in those patients with the more extensive tubular C5b-9 deposits. In conclusion, glomerular C5b-9 deposition seems to be secondary to the IgA and C3 deposition. In contrast, tubular C5b-9 is related to the numbers of interstitial T cells and MM. Activated interstitial mononuclear cells may lead to the tubular deposition of C5b-9, which eventually might contribute to the development of tubulointerstitial lesions (TIL) and renal function impairment.