RENAL CORTICAL COMPLEMENT C3 GENE-EXPRESSION IN IGA NEPHROPATHY

Glomerular C3 deposits are commonly found in immunoglobulin A (IgA) ne phropathy. Renal gene expression and protein synthesis of complement c omponents have been shown in settings of tissue inflammation. In this study, the pathogenetic involvement of locally produced C3 in IgA neph ropathy was analyzed. C3 gene expression was analyzed by reverse trans cription, polymerase chain reaction, and in situ hybridization techniq ues. C3 mRNA was detected in 56% of cases, with a significantly higher percentage in patients with moderate-to-severe lesions than in those with mild lesions (P < 0.01). By in situ hybridization, C3 transcript was predominantly expressed by tubular cells and some interstitial cel ls. C3 mRNA was also observed on glomerular parietal epithelial cells. Immunoreactive native C3 was detected on cortical tubuli by an anti-C 3c immunoallcaline-phosphatase technique. A significant correlation wa s found between renal C3 transcription and glomerulosclerosis, intraca pillary proliferation (both P < 0.005) and markers of interstitial dam age, including tubular atrophy (P < 0.05), interstitial infiltration ( P < 0.05), and fibrosis (P < 0.005). Proteinuria (P < 0.05), but not s erum creatinine, at the time of renal biopsy correlated with C3 mRNA. In conclusion, it was demonstrated that the C3 gene was expressed prim arily in proximal tubular cells and occasionally in glomerular crescen ts, and that its expression correlated with clinical and histologic ma rkers of severity and poor outcome of IgA nephropathy. Thus, a pathoge netic involvement of the local transcription and translation of the C3 gene in IgA nephropathy was suggested.