Exploring complement biomarkers in suspected axial spondyloarthritis.

Objectives: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals.
Methods: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg).
Results: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity.
Conclusions: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.
Competing Interests: Competing interests: CEM, AT, ST, AKW declare no conflicts of interest. AGL has received consulting fees from Novartis, UCB, Pfizer and Janssen; Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, UCB, Pfizer; Support for attending meetings from Janssen and Novartis; Participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Pfizer, UCB, Janssen. LS has received support for attending meetings and/or travel from Abbvie and MSD. MP has received support for attending meetings and/or travel from UCB and Jannsen; Receipt of equipment, materials, drugs, medical writing, gifts or other services from Novartis. VRR has received honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie; Support for attending meetings and/or travel from Pfizer; Participation on a Data Safety Monitoring Board or Advisory Board for Takeda. BM has received support for attending meetings and/or travel from UCB, Amgen and Galapagos Biopharma. JR has received support for attending meetings and/or travel from Abbvie, Jannsen, Novartis and UCB. SL has received support for attending meetings and/or travel from MSD and Abbvie. JS has received consulting fees from UCB; Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, MSD, Novartis, UCB. DP has received research grants from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer; Consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB; Participation on Advisory Board for AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: ASAS, GRAPPA. FP has received research grants from Novartis, Eli Lily, UCB; Consulting fees from AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Medscape, Galapagos, Hexal; Support for attending meetings and/or travel from Celgene, Janssen, Pfizer, Novartis, UCB; Participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Celgene, Janssen, Novartis, UCB; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: ASAS, Y-ASAS, GRAPPA, Y-GRAPPA, EMEUNET, EULAR, DGRh, DEGUM, Rheumazentrum Berlin; Receipt of study materials from Aidian Oy.
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