Work

Plasma C4d levels correlate with treatment response and renal activity in proliferative lupus nephritis

Year: 2025

Type: article

Abstract: OBJECTIVE: The investigation of complement factors in lupus nephritis (LN) in relation to treatment response and the impact of underlying genetics of C4. METHODS: Seventy-seven patients with active LN confirmed by a kidney biopsy and in whom second biopsies had been performed after immunosuppressive treatment were included. Complement factors C3, C4, C4d and C4d/C4 ratio were evaluated at the biopsy time points. The gene copy number variations of C4 (C4A and C4B) were also investigated. RESULTS: At baseline, 60 patients had class III/IV±V, proliferative LN (PLN) and 17 class V, membranous LN (MLN). Levels of C3 and C4 increased and C4d and C4d/C4 decreased after treatment (P < 0.0001), observed in treatment-responding PLN patients but not in MLN. C4d, C4 and C4d/C4 at second biopsies were associated with clinical response in PLN, and low C4d levels were found in PLN with histopathological response (P = 0.008). Renal activity index at second biopsies correlated to C4d and C4d/C4, but not to C3 or C4. C4 gene copy number variations were not associated with clinical or histopathological response. CONCLUSION: All complement markers were affected by immunosuppressive therapy and associated with response to therapy. Levels of C4d and C4d/C4 at follow-up biopsies showed a strong association with both clinical and histopathological response in PLN. The correlation with elevated C4d and C4d/C4 and persisting high activity index on repeated biopsies strengthens the findings on C4d as a promising biomarker for treatment response in PLN. The C4 genetic variations did not influence C4 levels or response to treatment.

Source: Lara D. Veeken

DOI: 10.1093/rheumatology/keaf160