{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:10:22Z","timestamp":1789467022524,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Background: Autoantibodies are central to the diagnosis and risk stratification of systemic sclerosis (SSc), but their prevalence and clinical associations may vary across populations. This study aimed to evaluate the prevalence and immuno-clinical associations of different autoantibodies in the Rheumatic Diseases Portuguese Register systemic sclerosis cohort. Methods: This was a multicentre observational registry-based study that used data from the Reuma.pt SSc module. Patients were divided according to autoantibody status, and associations between autoantibody expression and clinical data were assessed using appropriate statistical tests, with Bonferroni correction applied for multiple comparisons. Multivariable binary logistic regression was performed for clinically relevant outcomes, with adjustment for sex, age at diagnosis and disease duration. Results: A total of 1080 patients were included, 87.5% female, with a mean age at last evaluation of 60.2 \u00b1 14.6 years and a mean disease duration of 12.4 \u00b1 10.0 years. Limited cutaneous SSc was the most frequent clinical category (57.4%), followed by diffuse cutaneous SSc (17.7%), very early diagnosis of systemic sclerosis (VEDOSS; 12.3%), overlap syndromes (9.8%) and SSc sine scleroderma (2.8%). Antinuclear antibodies were present in 93.4% of patients. Anti-centromere antibodies (ACAs) were the most frequent SSc-specific autoantibodies (54.6%), followed by topoisomerase I antibodies (ATAs; 21.8%). ACA positivity was associated with limited cutaneous disease; older age at diagnosis; and lower frequency of interstitial lung disease (ILD), myositis and flexion contractures. ATA positivity was associated with diffuse cutaneous disease, male sex, higher modified Rodnan skin score (mRSS), digital ulcers, flexion contractures, oesophageal involvement and ILD. Among less frequent autoantibodies, anti-Pm\/Scl antibodies were associated with myositis, joint involvement, calcinosis and ILD; anti-U1RNP antibodies with younger age, MCTD overlap, myositis and joint involvement; anti-RNA polymerase III antibodies (ARAs) with scleroderma renal crisis and higher mRSS; anti-U3RNP antibodies with diffuse cutaneous disease and renal involvement; and anti-Ku antibodies with overlap syndromes. Conclusions: In this large real-world SSc cohort, autoantibody status was strongly associated with distinct clinical phenotypes, confirming its value for disease stratification. While most established immuno-clinical associations were reproduced, some differences from international cohorts were observed, supporting the need for population-specific validation of autoantibody associations in SSc.<\/jats:p>","DOI":"10.3390\/antib15050085","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"85","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence and Clinical Associations of Systemic Sclerosis-Related Autoantibodies: A Nationwide Reuma.pt Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Carolina","family":"Mazeda","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade da Regi\u00e3o de Aveiro, 3810-164 Aveiro, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o em Reumatologia de Aveiro, Centro Acad\u00e9mico Cl\u00ednico Egas Moniz, 3810-164 Aveiro, Portugal"},{"name":"EpiDoc Unit, NOVA Medical School, NOVA University Lisbon, 1169-056 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2186-2833","authenticated-orcid":false,"given":"Eduardo","family":"Dourado","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade da Regi\u00e3o de Aveiro, 3810-164 Aveiro, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o em Reumatologia de Aveiro, Centro Acad\u00e9mico Cl\u00ednico Egas Moniz, 3810-164 Aveiro, Portugal"},{"name":"Unidade de Investiga\u00e7\u00e3o em Reumatologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, CAML, 1649-028 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Almada Seixal, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Martins","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Reumatologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, CAML, 1649-028 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8970-6741","authenticated-orcid":false,"given":"Liliana","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade Viseu D\u00e3o-Laf\u00f5es, 3504-509 Viseu, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1562-4022","authenticated-orcid":false,"given":"T\u00e2nia","family":"Santiago","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research, Faculdade de Medicina, Universidade de Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4983-0833","authenticated-orcid":false,"given":"Francisca","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade do Alto Minho, 4990-078 Ponte de Lima, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Braga, 4710-243 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3123-4312","authenticated-orcid":false,"given":"Diogo Esperan\u00e7a","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Braga, 4710-243 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Dinis","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade da Guarda, 6300-858 Guarda, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-8357","authenticated-orcid":false,"given":"Ana Sofia","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade da Guarda, 6300-858 Guarda, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Daniel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade da Regi\u00e3o de Leiria, 2410-197 Leiria, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-0491","authenticated-orcid":false,"given":"In\u00eas","family":"Genrinho","sequence":"additional","affiliation":[{"name":"Pain Unit, Unidade Local de Sa\u00fade da Regi\u00e3o de Aveiro, 3810-164 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-1204","authenticated-orcid":false,"given":"Maura","family":"Couto","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade Viseu D\u00e3o-Laf\u00f5es, 3504-509 Viseu, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00edlia","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade da Regi\u00e3o de Leiria, 2410-197 Leiria, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jo\u00e3o","family":"Salvador","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research, Faculdade de Medicina, Universidade de Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-2425","authenticated-orcid":false,"given":"Ana Catarina","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Almada Seixal, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0647-6742","authenticated-orcid":false,"given":"Ana","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Almada Seixal, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-1365","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Santos","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Reumatologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, CAML, 1649-028 Lisboa, Portugal"},{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Almada Seixal, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Eurico","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Reumatologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, CAML, 1649-028 Lisboa, Portugal"},{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Lisboa Norte, Centro Acad\u00e9mico de Medicina de Lisboa (CAML), 1649-035 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Resende","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Reumatologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, CAML, 1649-028 Lisboa, Portugal"},{"name":"Department of Rheumatology, Unidade Local de Sa\u00fade de Lisboa Norte, Centro Acad\u00e9mico de Medicina de Lisboa (CAML), 1649-035 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Reumatologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, CAML, 1649-028 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15002","DOI":"10.1038\/nrdp.2015.2","article-title":"Systemic sclerosis","volume":"1","author":"Allanore","year":"2015","journal-title":"Nat. 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