Activated complement C3: a potentially novel predictor of progressive IgA nephropathy

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are systemic vasculitides.
• A reliable serologic marker for disease activity in these conditions is needed.
• The complement system, particularly the alternative pathway, is implicated in IgAN pathogenesis.

Purpose of the Study:

• To investigate activated C3 (actC3), C4-C3 complexes, and soluble C5b-9 (sC5b-9) as potential serologic markers of disease activity.
• To assess the correlation between complement activation markers and disease severity in IgAN.
• To evaluate actC3 as a predictor of renal function deterioration in IgAN.

Main Methods:

• Plasma samples from IgAN (N=50), HSP (N=4), and control patients (N=20) were analyzed.
• Concentrations of actC3, C4-C3 complexes, and sC5b-9 were measured.
• Clinical data including proteinuria, hematuria, renal function, and hypertension were collected and correlated with marker levels.

Main Results:

• Elevated actC3 levels were found in 30% of IgAN patients and one HSP patient, compared to controls.
• C4-C3 complexes were elevated in only 8% of IgAN patients; sC5b-9 levels were normal in all patients.
• In IgAN, higher actC3 levels correlated with increased proteinuria and hematuria.
• Elevated actC3 at presentation predicted subsequent renal function decline in IgAN patients (r = -0.56).

Conclusions:

• Alternative pathway complement activation is present in IgAN and HSP.
• Complement activation, indicated by actC3, is associated with more severe renal disease in IgAN.
• actC3 shows potential as a clinical marker for predicting IgAN disease course and renal function loss.