Differential complement pathways and components in the clinical spectrum of systemic lupus erythematosus

The precise contributions of the classical (CP), lectin (LP), and alternative (AP) pathways to systemic lupus erythematosus (SLE) remain incompletely understood. This study aimed to comprehensively investigate complement pathway components in SLE.

Sixty SLE patients and 20 healthy controls (HC) were recruited. Plasma C1q, C4, C4b, C2, C3, C5, Factor B (FB), Factor P (FP), Factor D (FD), Factor H (FH), Factor I (FI), and Mannose-binding lectin were measured by Multiplex Assay.

Compared to HC and patients with low disease activity, active SLE showed decreased C1q, C4, C4b, C3, and FP, with increased C2, while FB was reduced only relative to HC. Patients with low C3 and C4 showed higher anti-dsDNA and C2, more newly diagnosed SLE, and lower C1q, C5, FP, FB, and FH. SLE patients with isolated low C3 exhibited reduced FP, FB, and FH, with a trend toward longer disease duration. Newly diagnosed SLE showed decreased C1q and C4b, while those with renal involvement had lower C1q and C3 but higher C2. The concurrent infection subgroup presented decreased C1q and increased C2. Regression analysis identified C2 as independently associated with concurrent infection and FD as the strongest negative correlation with renal function. Principal component analysis further delineated three patient clusters with distinct complement signatures.

The CP is predominantly activated at disease onset, whereas the AP contributes to both initiation and progression of SLE. C2 and FD hold potential as biomarkers for SLE complications. Complement-driven stratification informs precision therapy in SLE.