Journal Article

AB0093 COMPLEMENT IN THE DIAGNOSIS OF AXIAL SPONDYLOARTHRITIS (AXSPA). INVESTIGATIONS IN A CROSS-SECTIONAL COHORT (OPTIREF) OF PATIENTS SUSPECTED OF AXIAL SPONDYLOARTHRITIS

Sieper, J., Spiller, L., Troldborg, A., Rios Rodriguez, V., Weber, A. K., Loft, A. G., Proft, F., Thiel, S., Muche, B., Mistegaard, C. E., Rademacher, J., Poddubnyy, D., Lueders, S.

2023

Overview

BackgroundAxial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease without specific diagnostic biomarkers. However, recent evidence suggests an involvement of the innate immune system in the pathogenesis of axSpA [1]. The lectin pathway of complement activation serves essential functions in the innate immune system, regulates homeostasis and development. We have previously shown the lectin pathway proteins (LPPs) L-ficolin and M-ficolin to be elevated in axSpA-patients compared with clinically relevant controls with unspecific low back pain (uLBP).ObjectivesTo investigate the diagnostic potential of LPP levels in patients recruited from a well-defined cross-sectional prospective cohort (OptiRef), including newly diagnosed axSpA-patients and uLBP-patients.MethodsSerum samples were obtained from 515 individuals from the OptiRef cohort; 151 newly diagnosed axSpA-patients and 364 uLBP-patients [2]. All patients were assessed according to a standardized protocol, incl. clinical information as demographics, SpA features, symptom duration, and disease activity. Routine lab tests (HLA-B27 and CRP) were performed. Imaging (x-ray and MRI) was performed if deemed clinically relevant. Serum levels of all 10 LPPs (MBL, CL-L1, M-ficolin, H-ficolin, L-ficolin, MASP-1, MASP-2, MASP-3, MAp19, and MAp44) and the complement activation product C3dg were measured by immunoassays.ResultsPatient characteristics are shown in Table 1. L-ficolin, MASP-2, and C3dg serum levels were increased in axSpA-patients compared with uLBP-patients, whereas CL-L1 and MASP-3 serum levels were decreased (Figure 1). After adjustments for CRP, C3dg serum levels remained significantly increased in axSpA-patients, whereas M-ficolin and MASP-3 serum levels were decreased in axSpA-patients. The diagnostic potential of combining either L-ficolin, MASP-3, and C3dg with HLA-B27 increased specificity to 93-95% compared with HLA-B27 alone (77%) but decreased sensitivity to 29-33% compared with HLA-B27 alone (83%). In a univariate logistic regression analysis, CL-L1, MASP-2, MASP-3, and C3dg were associated with an axSpA-diagnosis, and C3dg and MASP-3 remained significant in a multivariate logistic regression analysis.ConclusionIn this study, serum levels of C3dg, MASP-3, and CL-L1 differed significantly between axSpA-patients and uLBP-patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3, and C3dg increased diagnostic specificity for axSpA, it seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with the axSpA-diagnosis in multivariate logistic regression, indicating the complement system’s involvement in axSpA-pathogenesis. This should be further investigated.References[1]Ambarus, C., et al. Curr Opin Rheumatol. 2012[2]Poddubnyy, D., et al. Rheumatology (Oxford). 2021Table 1.Patient characteristics of the included patients from the OptiRef cohortTotal cohortn = 515axSpAn = 151uLBPn = 364p-value*Median age, years (IQR)36 (29-45)33 (26-40)38 (30-46)<0.001aMales, n (%)240 (47)83 (55)157 (43)0.008bHLA-B27 positive, n (%)203 (41)121 (83)θ82 (23)θθ<0.001bSmoking, n (%)138 (30)47 (31)91 (25)0.154bBMI, median (IQR)24 (22-27)24 (22-26)ϵ24 (22-28)ϵϵ0.464aSymptom duration, years median (IQR)6 (2-12)5 (2-10)7 (2-14)0.027aInflammatory back pain, n (%)210 (41)130 (86)175 (48)<0.001bGood response of back pain to NSAID, n (%)274 (73)102 (84)σ172 (68)σσ0.002bElevated CRP (> 5 mg/L), n (%)91 (18)53 (35)Δ38 (10)ΔΔ<0.001bRadiographic axSpA, n (%)77 (59)ASDAS-CRP, median (IQR)2.7 (1.8-3.3)§BASDAI, median (IQR)4.6 (2.9-5.7)ω* axSpA vs. uLBP. a Mann Whitney U test. b Chi2 test. Notations in the table indicate available data. If no marks, data were available on all patients. θ n=146. θθ n=353 ϵ n=141. ϵϵ n=340. σ n=122. σσ n=252. Δ n=150.ΔΔ n=358. § n=142. ω n=148.Figure 1.Serum levels of significantly altered complement LPPs in the two patient groups.Acknowledgements:NIL.Disclosure of InterestsClara Elbæk Mistegaard: None declared, Anne Troldborg: None declared, Anne Gitte Loft: None declared, Steffen Thiel: None declared, Laura Spiller: None declared, Valeria Rios Rodriguez: None declared, Burkhard Muche: None declared, Judith Rademacher: None declared, Anne-Katrin Weber: None declared, Susanne Lueders: None declared, Joachim Sieper: None declared, Denis Poddubnyy: None declared, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, Lilly, UCB.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Arthritis / Back pain / Complement activation / Diagnosis / Histocompatibility antigen HLA / Homeostasis / Immune system / Inflammatory diseases / Innate immunity / Low back pain / M-ficolin / MASP-1 protein / MASP-2 protein / Nonsteroidal anti-inflammatory drugs / Pathogenesis / Patients / Regression analysis / Rheumatic diseases / Rheumatology / Scientific Abstracts / Serum levels / Spondyloarthritis