Complement dysregulation in lupus nephritis: interplay of hypocomplementemia and complement-directed autoantibodies

Complement dysregulation is a defining feature of lupus nephritis (LN), traditionally assessed by C3 and C4 levels. Emerging studies suggest that complement-directed autoantibodies may reflect an expanded autoreactive network that remains poorly defined. In this study, complement components and corresponding autoantibodies were assessed in sixty-nine treatment naïve renal biopsy-proven (2003 ISN/RPS) LN patients and fifty healthy controls using nephelometry, commercially available ELISA and in-house standardized ELISA. LN patients exhibited widespread hypocomplementemia, with reduced C3 (94.2%), C4 (84.1%), C1q (79.7%), complement factor H (CFH; 34.8%), complement factor B (CFB; 18.8%) and complement factor P/properdin (CFP; 65.2%) levels. Anti-C1q (62.3%) and anti-C3 (21.7%) autoantibodies predominated in LN patients. At the nominal significance level, hypocomplementemia and complement-directed autoantibodies significantly associated with disease activity, renal dysfunction, cytopenias, and nuclear autoantibodies (p < 0.05). Following Benjamini-Hochberg FDR correction, significant associations were retained among complement proteins, complement-directed autoantibodies, and nuclear autoantibodies (q < 0.05). These findings demonstrated that complement dysregulation in LN encompasses both hypocomplementemia and complement-directed autoantibodies, reflecting a systemic autoreactive immune network. Comprehensive complement profiling may provide additional clinical-serological information for LN assessment and improve disease monitoring.