Complement C3c Reflects Acute-Phase Response but Not Clinical Phenotype in Systemic Sclerosis: A Cross-Sectional Study

This study evaluated routinely measured serum complement C3c (C3c) and complement C4 (C4) in relation to systemic inflammation, clinical and immunological phenotypes, and patient-reported outcomes (PROs) in systemic sclerosis (SSc). Seventy SSc patients fulfilling the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria underwent same-day assessment including serum C3c, C4, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), autoantibodies, immunosuppressive therapy and PROs. Associations were analysed using Spearman correlations and linear regression. C3c correlated strongly with CRP (rho = 0.53, p < 0.001) and ESR (rho = 0.49, p < 0.001) and remained independently associated with CRP (regression coefficient β = 0.26 mg/L per mg/dL, 95% confidence interval [CI] 0.14–0.38, p < 0.001) and ESR (β = 0.32 mm/h per mg/dL, 95% CI 0.16–0.47, p < 0.001), explaining ~17% and 15% of their variance. C4 showed weaker correlations with CRP (rho = 0.37, p = 0.004) and ESR (rho = 0.29, p = 0.03). Neither C3c nor C4 correlated with IL-6, modified Rodnan skin score (mRSS), interstitial lung disease (ILD), gastrointestinal involvement, SSc subset, autoantibodies, immunosuppressive therapy or PROs. C3c and C4 levels were significantly lower in patients with secondary Sjögren’s disease (SjD) than SSc-only. Serum C3c reflects acute-phase response in SSc, paralleling CRP and ESR but not clinical phenotype or patient-perceived burden, whereas C4 provides only weaker, secondary information.