C3a, C5a Renal Expression and Their Receptors are Correlated to Severity of IgA Nephropathy
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BACKGROUND: IgA nephropathy (IgAN) is the most common primary kidney disease, often leading to chronic renal failure. Complement activation products C3a and C5a have broad pro-inflammatory potential through their receptors, C3aR and C5aR, and contribute to the pathogenesis of several inflammatory and autoimmune diseases, but their roles in IgAN are poorly defined. PURPOSE: This study aimed to establish correlations between renal C3a, C5a, C3aR, C5aR, or serum/urinary C3a, C5a with clinical features and renal histopathology in patients with IgAN. METHODS: Eighty-three patients with renal biopsy proven IgAN were investigated. Thirty patients fulfilled Haas's II, 30 fulfilled Haas's III and 23 fulfilled Haas's IV criteria. Deposition of C3a and C5a was assessed by immunohistochemistry. C3aR and C5aR mRNAs and proteins in kidney tissue were examined by real-time quantitative PCR (RT-qPCR) and immunohistochemical staining, respectively. C3a and C5a levels were quantified by ELISA in serum and urine samples of 30 IgAN patients, 10 control subjects and 10 septic patients. RESULTS: Renal C3a and C5a deposition and C3aR and C5aR expression increased with increasing grades of renal pathology in IgAN patients. They positively correlated with proteinuria and serum creatinine (SCr), but not serum C-reactive protein (CRP) or complement 3 (C3). Serum C3a and C5a increased to levels comparable to septic patients but did not differ among IgAN sub-groups. In contrast, urinary C3a and C5a increased significantly and correlated positively with renal pathological grades. CONCLUSIONS: In patients with IgAN, urinary and renal C3a and C5a and renal expression of C3aR and C5aR are significantly correlated with the activity and severity of renal injury. This observation warrants further study into the roles of C3a, C5a and their receptors in the pathogenesis of IgAN and as potential therapeutic targets.
