{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T13:52:44Z","timestamp":1793713964815,"version":"4.6.1"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007949","name":"Swedish Rheumatism Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010814","name":"Foundation for Assistance to Disabled People in Skane","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010814","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead\u2010based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n\u00a0=\u00a02,110), Swedish age\u2010 and sex\u2010matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98\u2013100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19\u201326%) of early RA patients seronegative for anti\u2013cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A multiplex immunoassay with peptides from disease\u2010related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42463-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42463","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T03:54:36Z","timestamp":1675137276000},"page":"1110-1119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Autoantibodies to <scp>Disease\u2010Related<\/scp> Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"75","author":[{"given":"Erik","family":"L\u00f6nnblom","sequence":"first","affiliation":[{"name":"Section of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-7549","authenticated-orcid":false,"given":"Monica","family":"Leu Agelii","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-8216","authenticated-orcid":false,"given":"Outi","family":"Sareila","sequence":"additional","affiliation":[{"name":"Section of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics Karolinska Institutet, Stockholm, and Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Section of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingze","family":"Xu","sequence":"additional","affiliation":[{"name":"Section of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Viljanen","sequence":"additional","affiliation":[{"name":"Department of Chemistry\u2010BMC Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingi\u00e4ld","family":"Hafstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Division of Gastroenterology and Rheumatology, Department of Medicine Huddinge Karolinska Institutet, and Rheumatology Unit, Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0217-5029","authenticated-orcid":false,"given":"Maria L. E.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Spenshult Research and Development Center, Halmstad, and Department of Clinical Sciences Lund, Rheumatology Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Bergstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Region V\u00e4stra G\u00f6taland Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Karin","family":"Hultg\u00e5rd Ekwall","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rudin","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7187-1477","authenticated-orcid":false,"given":"Alf","family":"Kastbom","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Department of Biochemical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-2048","authenticated-orcid":false,"given":"Christopher","family":"Sj\u00f6wall","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Department of Biochemical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart T. 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