{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:14:42Z","timestamp":1783332882548,"version":"3.54.6"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Undifferentiated connective tissue disease (UCTD) represents a systemic autoimmune condition characterized by clinical and serological features suggestive of defined connective tissue diseases (CTDs), yet it is insufficient to fulfil existing classification criteria. Despite increasing interest, long-term outcomes \u2212 particularly progression to defined CTDs \u2212 remain incompletely understood. This study aimed to evaluate the clinical outcomes of a UCTD cohort followed for at least 5\u00a0years and to identify baseline clinical and serological factors associated with an increased risk of evolution to a defined CTD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 658 patients were screened for this retrospective cohort study. After applying predefined eligibility criteria, 504 patients who met established UCTD definitions were included. Baseline clinical, laboratory, and serological characteristics were analysed. Two patient outcome groups were defined at a 5-year follow-up: those who evolved to a defined CTD and those who remained stable. Given the limited number of cases evolving to defined CTDs, group comparisons were performed using Student\u2019s t-test or the Mann\u2013Whitney U test rather than logistic regression. Autoantibodies were assessed using indirect immunofluorescence for antinuclear antibodies and validated immunoassays for anti-dsDNA, anti-Sm, anti-Ro\/SS-A, anti-La\/SS-B, anti-Scl-70, anticentromere, anti-U1RNP, anti-Jo1, rheumatoid factor, anticyclic citrullinated peptide antibodies, antiphospholipid antibodies (anti-\u03b22 glycoprotein I IgM\/IgG and anticardiolipin IgM\/IgG), and lupus anticoagulant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After a mean follow-up of 82\u00a0months, 102 of the 504 UCTD patients (20.2%) developed a defined CTD (37 with Sj\u00f6gren\u2019s disease, 35 with systemic lupus erythematosus, 12 with systemic sclerosis, 14 with rheumatoid arthritis, and 4 with mixed CTDs) within a follow-up period of at least 5\u00a0years. The most common clinical manifestations of UCTD included arthralgia, sicca symptoms, photosensitivity, oral aphthae, and Raynaud\u2019s phenomenon. Differentiation was significantly associated with features, such as a Schirmer test \u22645\u00a0mm (P\u2009=\u2009.007), anti-dsDNA (P\u2009=\u2009.001), anti-Ro\/SS-A (P\u2009&amp;lt;\u2009.001), and hypocomplementemia (P\u2009=\u2009.004). Multivariate analysis identified several disease-specific predictors, including anti-Ro\/SS-A for Sj\u00f6gren\u2019s disease and anti-dsDNA and hypocomplementemia for systemic lupus erythematosus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Approximately one-fifth of UCTD patients progressed to a defined CTD during long-term follow-up, most frequently to Sj\u00f6gren\u2019s disease or systemic lupus erythematosus. Anti-Ro\/SS-A, anti-dsDNA, and a Schirmer test \u22645\u00a0mm were significant predictors of progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/mr\/roag006","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:45:33Z","timestamp":1770813933000},"page":"619-626","source":"Crossref","is-referenced-by-count":0,"title":["Can baseline features predict progression to defined connective tissue disease? Insights from a minimum 5-year follow-up study of 504 patients with undifferentiated connective tissue disease: A retrospective study"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7219-1457","authenticated-orcid":false,"given":"Hakan","family":"Apaydin","sequence":"first","affiliation":[{"name":"Clinical of Rheumatology, Ankara Etlik City Hospital , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-5488","authenticated-orcid":false,"given":"\u015eerife \u00c7o\u015fkun","family":"Sa\u011firkaya","sequence":"additional","affiliation":[{"name":"Clinical of Rheumatology, Ankara Bilkent City Hospital , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-8142","authenticated-orcid":false,"given":"B\u00fcnyamin","family":"Polat","sequence":"additional","affiliation":[{"name":"Clinical of Rheumatology, Ankara Bilkent City Hospital , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4409-059X","authenticated-orcid":false,"given":"Berkan","family":"Arma\u011fan","sequence":"additional","affiliation":[{"name":"Clinical of Rheumatology, Ankara Bilkent City Hospital , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2582-7445","authenticated-orcid":false,"given":"Ahmet","family":"Omma","sequence":"additional","affiliation":[{"name":"Clinical of Rheumatology, University of Health Sciences , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-8365","authenticated-orcid":false,"given":"\u015e\u00fckran","family":"Erten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Y\u0131ld\u0131r\u0131m Beyaz\u0131t University Medical School , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4109-0642","authenticated-orcid":false,"given":"Orhan","family":"K\u00fc\u00e7\u00fck\u015fahin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Y\u0131ld\u0131r\u0131m Beyaz\u0131t University Medical School , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1965-9756","authenticated-orcid":false,"given":"Serdar Can","family":"G\u00fcven","sequence":"additional","affiliation":[{"name":"Clinical of Rheumatology, Ankara Bilkent City Hospital , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"2026070605221586300_ref1","first-page":"615","article-title":"Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria","volume":"17","author":"Mosca","year":"1999","journal-title":"Clin Exp Rheumatol"},{"key":"2026070605221586300_ref2","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.berh.2007.09.004","article-title":"Undifferentiated connective tissue diseases (UCTD): a new frontier for rheumatology","volume":"21","author":"Mosca","year":"2007","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2026070605221586300_ref3","first-page":"469","article-title":"Systemic lupus erythematosus: predictors of its occurrence among a cohort of patients with early undifferentiated connective tissue disease: multivariate analyses and identification of risk factors","volume":"23","author":"Calvo-Alen","year":"1996","journal-title":"J Rheumatol"},{"key":"2026070605221586300_ref4","first-page":"403","article-title":"Undifferentiated connective tissue disease with antibodies to Ro\/SSa: clinical features and follow-up of 148 patients","volume":"19","author":"Cavazzana","year":"2001","journal-title":"Clin Exp Rheumatol"},{"key":"2026070605221586300_ref5","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum"},{"key":"2026070605221586300_ref6","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.1002\/art.38098","article-title":"Classification criteria for systemic sclerosis: an ACR-EULAR collaborative initiative","volume":"65","author":"Hoogen","year":"2013","journal-title":"Arthritis Rheum"},{"key":"2026070605221586300_ref7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/art.39859","article-title":"2016 ACR-EULAR classification criteria for primary Sj\u00f6gren\u2019s syndrome: a consensus and data-driven methodology involving three international patient cohorts","volume":"69","author":"Shiboski","year":"2016","journal-title":"Arthritis Rheumatol (Hoboken, NJ)"},{"key":"2026070605221586300_ref8","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1002\/art.40930","article-title":"2019 European League Against Rheumatism\/American College of Rheumatology classification criteria for systemic lupus erythematosus","volume":"71","author":"Aringer","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2026070605221586300_ref9","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1164\/rccm.200702-220OC","article-title":"Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease?","volume":"176","author":"Kinder","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026070605221586300_ref10","first-page":"213","article-title":"Defining unclassifiable connective tissue diseases: incomplete, undifferentiated, or both?","volume":"32","author":"Doria","year":"2005","journal-title":"J Rheumatol"},{"key":"2026070605221586300_ref11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1080\/14397595.2019.1709944","article-title":"2019 diagnostic criteria for mixed connective tissue disease (MCTD): from the Japan research committee of the ministry of health, labor, and welfare for systemic autoimmune diseases","volume":"31","author":"Tanaka","year":"2021","journal-title":"Mod Rheumatol"},{"key":"2026070605221586300_ref12","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13075-023-02997-w","article-title":"Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis","volume":"25","author":"Kim","year":"2023","journal-title":"Arthritis Res Ther"},{"key":"2026070605221586300_ref13","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.berh.2012.01.005","article-title":"Undifferentiated CTD: a wide spectrum of autoimmune diseases","volume":"26","author":"Mosca","year":"2012","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2026070605221586300_ref14","first-page":"313","article-title":"Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD)","volume":"21","author":"Bodolay","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"2026070605221586300_ref15","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1007\/s00296-011-2234-y","article-title":"Undifferentiated connective tissue disease in a rheumatology center in Cali, Colombia: clinical features of 94 patients followed for a year","volume":"33","author":"Guerrero","year":"2013","journal-title":"Rheumatol Int"},{"key":"2026070605221586300_ref16","first-page":"739","article-title":"Undifferentiated connective tissue disease: predictors of evolution into definite disease","volume":"35","author":"Garc\u00eda-Gonz\u00e1lez","year":"2017","journal-title":"Clin Exp Rheumatol"},{"key":"2026070605221586300_ref17","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1007\/s10238-025-01614-1","article-title":"Undifferentiated connective tissue disease: the diagnoses critically revised-experience of a single center","volume":"25","author":"Cavazzana","year":"2025","journal-title":"Clin Exp Med"},{"key":"2026070605221586300_ref18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/BF01451046","article-title":"Undifferentiated connective tissue disease: natural history and evolution into definite CTD assessed in 84 patients initially diagnosed as early UCTD","volume":"17","author":"Danieli","year":"1998","journal-title":"Clin Rheumatol"},{"key":"2026070605221586300_ref19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jaut.2014.01.019","article-title":"The diagnosis and classification of undifferentiated connective tissue diseases","volume":"48","author":"Mosca","year":"2014","journal-title":"J Autoimmun"},{"key":"2026070605221586300_ref20","doi-asserted-by":"crossref","first-page":"869172","DOI":"10.3389\/fimmu.2022.869172","article-title":"Precursors to systemic sclerosis and systemic lupus erythematosus: from undifferentiated connective tissue disease to the development of identifiable connective tissue diseases","volume":"13","author":"Martin Calderon","year":"2022","journal-title":"Front Immunol"},{"key":"2026070605221586300_ref21","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.1002\/1521-4141(200012)30:12<3575::AID-IMMU3575>3.0.CO;2-#","article-title":"Study group on incomplete SLE and SLE with disease duration longer than 10 years","volume":"30","author":"Moscato","year":"2000","journal-title":"Eur J Immunol"},{"key":"2026070605221586300_ref22","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1177\/0961203306069352","article-title":"Clinical and prognostic value of autoantibodies in Puerto Ricans with systemic lupus erythematosus","volume":"15","author":"Vil\u00e1","year":"2006","journal-title":"Lupus"},{"key":"2026070605221586300_ref23","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.autrev.2014.11.002","article-title":"Undifferentiated connective tissue disease at risk for systemic sclerosis (SSc)(so far referred to as very early\/early SSc or pre-SSc)","volume":"14","author":"Valentini","year":"2015","journal-title":"Autoimmun Rev"},{"key":"2026070605221586300_ref24","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.1016\/j.autrev.2014.11.002","article-title":"Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis","volume":"58","author":"Koenig","year":"2008","journal-title":"Arthritis Rheum Off J Am Coll Rheumatol"},{"key":"2026070605221586300_ref25","doi-asserted-by":"publisher","first-page":"102659","DOI":"10.1016\/j.autrev.2020.102659","article-title":"Undifferentiated connective tissue disease at risk for systemic sclerosis: which patients might be labeled prescleroderma?","volume":"19","author":"Valentini","year":"2020","journal-title":"Autoimmun Rev"},{"key":"2026070605221586300_ref26","first-page":"229","article-title":"Undifferentiated connective tissue disease: clinical and serological profile of 578 patients followed for five years: disease course, prognosis and therapy","volume":"143","author":"Bodolay","year":"2002","journal-title":"Orv Hetil"},{"key":"2026070605221586300_ref27","doi-asserted-by":"publisher","first-page":"103184","DOI":"10.1016\/j.autrev.2022.103184","article-title":"Predicting progression from undifferentiated connective tissue disease to definite connective tissue disease: a systematic review and meta-analysis","volume":"21","author":"Dyball","year":"2022","journal-title":"Autoimmun Rev"},{"key":"2026070605221586300_ref28","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1007\/s11926-023-01099-5","article-title":"Undifferentiated connective tissue disease: comprehensive review","volume":"25","author":"Rubio","year":"2023","journal-title":"Curr Rheumatol Rep"}],"container-title":["Modern Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mr\/advance-article-pdf\/doi\/10.1093\/mr\/roag006\/66850838\/roag006.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/36\/4\/619\/66850838\/roag006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/36\/4\/619\/66850838\/roag006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T09:23:06Z","timestamp":1783329786000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mr\/article\/36\/4\/619\/8472599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2,11]]},"published-print":{"date-parts":[[2026,6,30]]}},"URL":"https:\/\/doi.org\/10.1093\/mr\/roag006","relation":{},"ISSN":["1439-7595","1439-7609"],"issn-type":[{"value":"1439-7595","type":"print"},{"value":"1439-7609","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,2,11]]}}}