Relationship of complement activation route with clinical manifestations in Japanese patients with systemic lupus erythematosus: A retrospective observational study

Objectives. To assess the relationship between the complement activation route and clinical manifestations in systemic lupus erythematosus (SLE). Methods. Patients with SLE in whom complement activation occurred were divided into two groups: those in whom the complement system was mainly activated through the classical pathway (low serum C3 and C4 levels; CP group); and those in whom the complement system was solely activated through the alternative pathway (low serum C3 with normal C4 levels; AP group). Clinical manifestations were compared between the groups. Results. The CP group had higher frequencies of arthritis, serositis, and nephritis, and a higher prevalence of anti-DNA antibodies compared to the AP group (arthritis: 50.0% vs. 13.0%, p = 0.0014; serositis: 37.5% vs. 13.0%, p = 0.0257; nephritis: 63.6% vs. 21.7%, p = 0.0003; anti-DNA antibodies: 73.9% vs. 30.4%, p = 0.0001). In contrast, the AP group had a higher frequency of antiphospholipid (anti-PL) antibodies and a higher prevalence of antiphospholipid syndrome (APS) (anti-PL antibodies: 70.6% vs. 37.3%, p = 0.0136; APS: 39.1% vs. 5.7%, p < 0.0001). Conclusions. Our results suggest that a different complement system mechanism may act in the pathogenesis of APS in patients with SLE.