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The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjo\u0308gren\u2019s syndrome (SS), and healthy controls to identify candidate biomarker signatures for differential classification. A total of 316 serum samples collected from patients with SLE, RA, SS, or SV and from healthy controls were analyzed using 394-plex recombinant antibody microarrays. Differential protein expression profiling was examined using Wilcoxon signed rank test, and condensed biomarker panels were identified using advanced bioinformatics and state-of-the art classification algorithms to pinpoint signatures reflecting each disease (raw data set available at https:\/\/figshare.com\/s\/3bd3848a28ef6e7ae9a9.). In this study, we were able to classify the included individual IRDs with high accuracy, as demonstrated by the ROC area under the curve (ROC AUC) values ranging between 0.96 and 0.80. In addition, the groups of IRDs could be separated from healthy controls at an ROC AUC value of 0.94. Disease-specific candidate biomarker signatures and general autoimmune signature were identified, including several deregulated analytes. This study supports the rationale of using multiplexed affinity-based technologies to reflect the biological complexity of autoimmune diseases. A multiplexed approach for decoding multifactorial complex diseases, such as autoimmune diseases, will play a significant role for future diagnostic purposes, essential to prevent severe organ- and tissue-related damage.<\/jats:p>","DOI":"10.1021\/acs.jproteome.0c00657","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T15:42:31Z","timestamp":1608738151000},"page":"1252-1260","source":"Crossref","is-referenced-by-count":18,"title":["Proteomic Data\nAnalysis for Differential Profiling\nof the Autoimmune Diseases SLE, RA, SS, and ANCA-Associated Vasculitis"],"prefix":"10.1021","volume":"20","author":[{"given":"Mattias","family":"Ohlsson","sequence":"first","affiliation":[{"name":"Lund University , , So\u0308lvegatan 14A , ,","place":["Lund, Sweden, SE-221 00"]},{"name":"Halmstad University , , ,","place":["Halmstad, Sweden, SE-301 18"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hellmark","sequence":"additional","affiliation":[{"name":"Sk\u00e5ne University Hospital Lund, Lund University , , ,","place":["Lund, Sweden, SE-221 85"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders A.","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"Lund University , , ,","place":["Lund, Sweden, SE-221 00"]},{"name":"Sk\u00e5ne University Hospital , , ,","place":["Lund and Malmo\u0308, Sweden, SE-214 28"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Theander","sequence":"additional","affiliation":[{"name":"Lund University , , ,","place":["Malmo\u0308, Sweden, SE-221 00"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Turesson","sequence":"additional","affiliation":[{"name":"Sk\u00e5ne University Hospital , , ,","place":["Lund and Malmo\u0308, Sweden, SE-214 28"]},{"name":"Lund University , , ,","place":["Malmo\u0308, Sweden, SE-221 00"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Klint","sequence":"additional","affiliation":[{"name":"Immunovia AB , ,","place":["Lund, Sweden, 223 81"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christer","family":"Wingren","sequence":"additional","affiliation":[{"name":"Lund University, Medicon Village , , Scheeleva\u0308gen 2 , ,","place":["Lund, Sweden, SE-223 81"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6651-7091","authenticated-orcid":true,"given":"Anna Isinger","family":"Ekstrand","sequence":"additional","affiliation":[{"name":"Lund University, Medicon Village , , Scheeleva\u0308gen 2 , ,","place":["Lund, Sweden, SE-223 81"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"2026090223354967300_cit1","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.2105\/AJPH.2009.180273","article-title":"Burden\nof mortality associated with autoimmune diseases among females in\nthe United Kingdom","volume":"100","author":"Thomas","year":"2010","journal-title":"Am. 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Public Health"},{"key":"2026090223354967300_cit3","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1002\/art.20093","article-title":"Sjogren\u2019s\nsyndrome associated with systemic lupus erythematosus: clinical and\nlaboratory profiles and comparison with primary Sjogren\u2019s syndrome","volume":"50","author":"Manoussakis","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2026090223354967300_cit4","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1186\/s13075-014-0489-x","article-title":"Shared signatures between rheumatoid\narthritis, systemic lupus erythematosus and Sjogren\u2019s syndrome\nuncovered through gene expression meta-analysis","volume":"16","author":"Toro-Domi\u0301nguez","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"2026090223354967300_cit5","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1093\/rheumatology\/kew023","article-title":"Previous\ndiagnosis of Sjogren\u2019s\nSyndrome as rheumatoid arthritis or systemic lupus erythematosus","volume":"55","author":"Rasmussen","year":"2016","journal-title":"Rheumatology"},{"key":"2026090223354967300_cit6","first-page":"239","article-title":"Ro(SSA)\nand La(SSB) antibodies in the clinical spectrum of Sjogren\u2019s\nsyndrome","volume":"9","author":"Alexander","year":"1982","journal-title":"J. Rheumatol."},{"key":"2026090223354967300_cit7","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1056\/NEJM198806233182504","article-title":"Anti-neutrophil cytoplasmic autoantibodies\nwith specificity\nfor myeloperoxidase in patients with systemic vasculitis and idiopathic\nnecrotizing and crescentic glomerulonephritis","volume":"318","author":"Falk","year":"1988","journal-title":"N. Engl. J. 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A."},{"key":"2026090223354967300_cit29","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.005033","article-title":"Serum protein profiling\nof systemic lupus erythematosus and systemic sclerosis using recombinant\nantibody microarrays","volume":"10","author":"Carlsson","year":"2011","journal-title":"Mol. Cell. Proteomics"},{"key":"2026090223354967300_cit30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate:\na practical and\npowerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R.\nStat. Soc., Ser. 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Med. J."},{"key":"2026090223354967300_cit38","doi-asserted-by":"publisher","first-page":"3527","DOI":"10.1021\/pr070204f","article-title":"Design of recombinant\nantibody microarrays for serum protein profiling: targeting of complement\nproteins","volume":"6","author":"Ingvarsson","year":"2007","journal-title":"J. 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Autoimmun."},{"key":"2026090223354967300_cit43","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1146\/annurev.biochem.70.1.503","article-title":"Mechanisms\nunderlying ubiquitination","volume":"70","author":"Pickart","year":"2001","journal-title":"Annu. Rev. Biochem."},{"key":"2026090223354967300_cit44","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/35056563","article-title":"Themes\nand variations on ubiquitylation","volume":"2","author":"Weissman","year":"2001","journal-title":"Nat. Rev.\nMol. Cell Biol."},{"key":"2026090223354967300_cit45","doi-asserted-by":"publisher","first-page":"6277","DOI":"10.4049\/jimmunol.176.10.6277","article-title":"The Sjogren\u2019s\nsyndrome-associated autoantigen Ro52 is an E3 ligase that regulates\nproliferation and cell death","volume":"176","author":"Espinosa","year":"2006","journal-title":"J. Immunol."},{"key":"2026090223354967300_cit46","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1146\/annurev.immunol.19.1.163","article-title":"Anti-TNF alpha therapy\nof rheumatoid arthritis: what\nhave we learned?","volume":"19","author":"Feldmann","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"2026090223354967300_cit47","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1056\/NEJM200011303432202","article-title":"Anti-Tumor Necrosis\nFactor Trial in Rheumatoid Arthritis with Concomitant Therapy Study,\nG., Infliximab and methotrexate in the treatment of rheumatoid arthritis.\nAnti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant\nTherapy Study Group","volume":"343","author":"Lipsky","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"2026090223354967300_cit48","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","article-title":"Investigators, O., Effect of interleukin-6 receptor inhibition with\ntocilizumab in patients with rheumatoid arthritis (OPTION study):\na double-blind, placebo-controlled, randomised trial","volume":"371","author":"Smolen","year":"2008","journal-title":"Lancet"},{"key":"2026090223354967300_cit49","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1056\/NEJMoa1613849","article-title":"Trial of Tocilizumab\nin Giant-Cell Arteritis","volume":"377","author":"Stone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"2026090223354967300_cit50","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s00005-014-0294-x","article-title":"Role of osteopontin\nin systemic lupus erythematosus","volume":"62","author":"Kaleta","year":"2014","journal-title":"Arch. Immunol.\nTher. Exp."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.0c00657","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/20\/2\/1252\/67116565\/acs.jproteome.0c00657.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/20\/2\/1252\/67116565\/acs.jproteome.0c00657.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:38:02Z","timestamp":1788406682000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/20\/2\/1252\/454394\/Proteomic-Data-Analysis-for-Differential-Profiling"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,23]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,12,23]]},"published-print":{"date-parts":[[2021,2,5]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.0c00657","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,23]]}}}