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Antibodies to CII appear around the clinical onset of the autoimmune disease rheumatoid arthritis (RA) in a subset of patients. They target specific epitopes on CII and can be pathogenic or protective. Assays for early detection of such autoantibodies may provide new opportunities for selecting effective treatment strategies of RA. We report the efficient and reproducible assembly of an array of covalently branched native and citrullinated triple helical peptides (THPs) from CII that contain defined autoantibody epitopes. Both monoclonal antibodies and sera from experimental mouse models show a unique reactivity toward the THPs, compared to cyclic peptides containing the epitopes, revealing the importance that the epitopes are displayed in a triple-helical conformation. Importantly, antibodies against three of the THPs that contain major CII epitopes were found to be increased in sera from patients with RA, compared to control persons. These results indicate that such synthetic THPs should be included in multiplex analysis of autoantibodies that are uniquely occurring in individuals with early RA, to provide valuable information on disease prognosis and on what type of therapy should be chosen for individual patients.<\/jats:p>","DOI":"10.1021\/acschembio.0c00680","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T09:28:29Z","timestamp":1599730109000},"page":"2605-2615","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis of an Array of Triple-Helical Peptides from\nType II Collagen for Multiplex Analysis of Autoantibodies in Rheumatoid\nArthritis"],"prefix":"10.1021","volume":"15","author":[{"given":"Johan","family":"Viljanen","sequence":"first","affiliation":[{"name":"Uppsala University , , ,","place":["Uppsala, Sweden, SE-75123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lo\u0308nnblom","sequence":"additional","affiliation":[{"name":"Karolinska Institute , , ,","place":["Stockholm, Sweden, SE-17177"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changrong","family":"Ge","sequence":"additional","affiliation":[{"name":"Karolinska Institute , , ,","place":["Stockholm, Sweden, SE-17177"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Uppsala University , , ,","place":["Uppsala, Sweden, SE-75123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Karolinska Institute , , ,","place":["Stockholm, Sweden, SE-17177"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Aldi","sequence":"additional","affiliation":[{"name":"Karolinska Institute , , ,","place":["Stockholm, Sweden, SE-17177"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Cai","sequence":"additional","affiliation":[{"name":"Karolinska Institute , , ,","place":["Stockholm, Sweden, SE-17177"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alf","family":"Kastbom","sequence":"additional","affiliation":[{"name":"Linko\u0308ping University , , ,","place":["Linko\u0308ping, Sweden, SE-58185"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-2048","authenticated-orcid":true,"given":"Christopher","family":"Sjo\u0308wall","sequence":"additional","affiliation":[{"name":"Linko\u0308ping University , , ,","place":["Linko\u0308ping, Sweden, SE-58185"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"Gjertsson","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Academy, University of Gothenburg , , ,","place":["Gothenburg, Sweden, SE-40530"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikard","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"Karolinska Institute , , ,","place":["Stockholm, Sweden, SE-17177"]},{"name":"The Second Affiliated Hospital of Xi\u2019an Jiaotong University (Xibei Hospital) , ,","place":["Xi\u2019an, China, 710004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-6040","authenticated-orcid":true,"given":"Jan","family":"Kihlberg","sequence":"additional","affiliation":[{"name":"Uppsala University , , ,","place":["Uppsala, Sweden, SE-75123"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"2026081714190418400_cit1","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"Mechanisms of Disease:\nThe Pathogenesis of Rheumatoid\nArthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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Chem."},{"key":"2026081714190418400_cit29","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1136\/annrheumdis-2012-201484","article-title":"Genetic and environmental determinants\nfor disease\nrisk in subsets of rheumatoid arthritis defined by the anticitrullinated\nprotein\/peptide antibody fine specificity profile","volume":"72","author":"Lundberg","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"2026081714190418400_cit30","doi-asserted-by":"publisher","first-page":"R949","DOI":"10.1186\/ar1767","article-title":"Antibodies to citrullinated proteins\nand differences in clinical progression of rheumatoid arthritis","volume":"7","author":"van\nder Helm-van Mil","year":"2005","journal-title":"Arthritis Res. 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Soc."},{"key":"2026081714190418400_cit46","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1002\/art.39170","article-title":"Associations with smoking and shared\nepitope differ between IgA- and IgG-class antibodies to cyclic citrullinated\npeptides in early rheumatoid arthritis","volume":"67","author":"Svard","year":"2015","journal-title":"Arthritis\nRheumatol."},{"key":"2026081714190418400_cit47","doi-asserted-by":"publisher","first-page":"8","DOI":"10.2174\/1874312901409010008","article-title":"Comparing Five Year Out-Come in Two\nCohorts of Patients with Early Rheumatoid Arthritis - A BARFOT Study","volume":"9","author":"Andersson","year":"2015","journal-title":"Open Rheumatol. J."},{"key":"2026081714190418400_cit48","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1080\/14034940210133771","article-title":"Invitation\nto a population-based\ncohort study: differences between subjects recruited using various\nstrategies","volume":"30","author":"Manjer","year":"2002","journal-title":"Scand. J. Public Health"},{"key":"2026081714190418400_cit49","doi-asserted-by":"publisher","first-page":"2657","DOI":"10.1074\/mcp.M112.026757","article-title":"Autoantibody\nProfiling in Multiple\nSclerosis Using Arrays of Human Protein Fragments","volume":"12","author":"Ayoglu","year":"2013","journal-title":"Mol. Cell. 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