Background. Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by inflammatory pathways involving cytokines and complement activation. Interleukin-6 (IL-6) promotes hepatic synthesis of acute-phase proteins, including complement components C3 and C4. Tocilizumab (TCZ), a humanized monoclonal antibody targeting the IL-6 receptor, has proven effective in RA management. However, its impact on the complement system remains poorly characterized. Methods and Results. We studied 10 patients with moderate-to-severe RA treated with intravenous TCZ (8 mg/kg/month) over 48 weeks. Serum levels of C3, C4, CH50, ESR, and CRP were assessed at baseline and at 4, 12, 24, 36, and 48 weeks. Complement activation was monitored via C3 and factor B split products. A rapid and sustained reduction in C3 and C4 levels was observed starting at week 4, without changes in CH50 or detectable cleavage products. This reduction coincided with significant improvement in inflammatory markers and clinical outcomes (DAS28 and HAQ scores). Conclusions. IL-6R blockade with TCZ is associated with a rapid and sustained reduction in complement proteins C3 and C4. In a proportion of patients, complement levels reached values below the lower limit of normal during follow-up, while CH50 remained stable and complement split products were not detected. These findings are consistent with altered acute-phase/hepatic regulation of complement under IL-6 inhibition rather than overt complement consumption. The clinical significance of complement reduction and its role as a biomarker of treatment response require confirmation in larger studies.

Scilight Press

Articles

Journal of Mosaic of Autoimmunity

About Scilight

Journals

Publishing Policies

Contact Us