Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT

Objectives: To investigate lectin pathway proteins (LPPs) and complement activation marker C3dg as biomarkers for disease activity and treatment response in a multicentre, randomized controlled trial of axial spondyloarthritis (axSpA) patients initiating TNF inhibitor (TNFi) therapy.<br/><br/>Methods: Serum samples from 108 patients with active radiographic axSpA from the CONSUL study, collected before and after 12 weeks of TNFi therapy, were measured using immunoassays for LPPs (MBL, CL-L1, M-, L-, and H-ficolin, MASP-1, -2, and -3, MAp44) and the complement activation marker C3dg.<br/><br/>Results: After 12 weeks of TNFi therapy, serum levels of LPPs L-ficolin, M-ficolin, and MASP-2 decreased, while MASP-3 increased after adjustment for baseline CRP. Baseline L-ficolin levels correlated positively with baseline ASDAS-CRP and BASFI. C3dg correlated positively with ASDAS-CRP. Conversely, MASP-1 and MAp44 correlated negatively with ASDAS-CRP. Assessed by univariate logistic regression, C3dg and MASP-1 were associated with treatment response of clinically important improvement (ΔASDAS-CRP ≥1.1) and inactive disease (ASDAS-CRP &lt;1.3) at week 12, respectively. Only C3dg remained significant in a multivariate regression analysis.<br/><br/>Conclusion: In this study, complement LPPs L-ficolin, M-ficolin, and MASP-2 levels decrease following initiation of TNFi therapy, whereas alternative pathway critical component MASP-3 increases. Baseline L-ficolin and C3dg correlated positively with ASDAS-CRP, potentially by CRP influence. Nevertheless, baseline C3dg levels were associated with treatment response (ASDAS-CRP &lt;1.3) at week 12. Our results provide important perspectives on the inflammatory processes in axSpA, shedding light on the involvement of the complement system related to disease activity, treatment response, and potentially to prognosis.