Antibodies to post-translationally modified collagen ii in spondyloarthritis

Background: Spondyloarthritis (SpA) are a group of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints, or predominantly peripheral arthritis. The most common axial SpA (axSpA) are non-radiographic axSpA and in particular ankylosing spondylitis. The current gold standard diagnostic criteria for axSpA are clinical symptoms, radiology, MRI or ultrasound according to Assessment of SpondyloArthritis international Society (ASAS) criteria. We have previously showed that antibodies to oxidative post-translationally modified collagen type II (oxPTM-CII) are present and specific in RA patients whether ACPA positive or negative. Objectives: The aim of the current study was to test the presence of antibody to oxidised collagen type II (CII) in axSpA, based on the hypothesis that spinal inflammation in axial SpA results in oxidative posttranslational modification (oxPTM) of axial joints cartilage matrix proteins such as CII with the consequently formation of neoepitopes and a secondary humoral autoimmune response. Methods: CII was oxidised by exposing CII to ribose and hypochlorous acid. Levels of antibodies specific to native CII and CII post-translationally modified by oxidants (oxPTM-CII) was assessed by enzyme-linked immunosorbent assays (ELISA) in serum samples obtained from patients with axSpA (n=67) in remission and axSpA patients (n=14) non in remission. Reactivity in axSpA was compared to reactivity in samples from patients with predominantly peripheral arthritis such as psoriatic arthritis (PsA, n=54)), undifferentiated arthritis (UA, n=49) and early rheumatoid arthritis (ERA, n=60). As a control we used fibromyalgia (FM, n=19) and healthy subjects (HC, n=70). The specificity of the binding was further assessed by competitive ELISA and western blot. Results: Stronger binding to oxPTM-CII was observed in serum samples from axSpA patients, the positivity was 72% for patients in remission and 86% for patients not in remission (86%) compare to positivity in PsA group (33%), UA group (35%) and FM group (16%), (p<0.0001). Interestingly, binding of axSpA samples was similar to binding of serum samples from ERA (95%). Binding to ROS-CII was directed to a range of ROS-CII fragments between 25 and 150 kDa. Conclusions: Formation of oxPTM-CII neoantigens in the inflamed axial joints results in an immune response that elicits antibodies specific to oxPTM-CII. Once established in future studies, antibodies to oxPTM-CII may be developed as potential biomarker for axSpA. References: J. Braun, J. Sieper .“Ankylosing spondylitis.” Lancet 2007;369(9570):1379–1390. Strollo R, Ponchel F, Malmström V, Rizzo P, Bombardieri M, Wenham CY, Landy R, Perret D, Watt F, Corrigall VM, Winyard PG, Pozzilli P, Conaghan PG, Panayi GS, Klareskog L, Emery P, Nissim A. Autoantibodies to posttranslationally modified type II collagen as potential biomarkers for rheumatoid arthritis. Arthritis Rheum 2013 July;65(7):1702–12. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2018-eular.4404 Citation: Ann Rheum Dis, volume 77, supplement Suppl, year 2018, page A622Session: Spondyloarthritis – etiology, pathogenesis and animal models