Activation of the acute phase response and complement C3 in patients with IgA nephropathy

Abstract

Recently we showed systemic complement activation in patients with immunoglobulin A (IgA) nephropathy (measured by "activated C3" [actC3], in other words, neoantigens developing on breakdown products after C3 activation) and reported that plasma levels of actC3 can indicate disease activity and renal outcome. In this study we investigated whether plasma C3a and C-reactive protein (CRP), which require tests that are more readily available, have a similar diagnostic and predictive value. CRP was measured using a highly sensitive enzyme-linked immunosorbent assay and C3a using a specific immunoassay. CRP and C3a levels were significantly higher in 56 patients with IgA nephropathy as compared with 55 healthy controls. C3a levels in IgA nephropathy patients were also significantly increased in comparison with 42 patients with hypertension or nonimmune renal diseases. Neither C3a nor CRP levels correlated with those of actC3 in IgA nephropathy patients. We also compared 10 IgA nephropathy patients with stable, normal renal function with eight IgA nephropathy patients progressing from normal to impaired renal function during mean follow-ups of 7.1 and 5.1 years, respectively. Mean CRP but not C3a levels during the observation period were significantly higher in IgA nephropathy patients with disease progression than in those with stable renal function. Systemic complement activation can be detected by measurement of plasma C3a in IgA nephropathy, but C3a levels cannot substitute for actC3 in predicting renal prognosis. Subclinical induction of the acute phase response is also present in patients with progressive IgA nephropathy, but again its prognostic value is limited. Repeated determinations performed over prolonged time courses may possibly improve the prognostic value of CRP levels.