{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:43:34Z","timestamp":1790621014709,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Greece","award":["MIS-5000432"],"award-info":[{"award-number":["MIS-5000432"]}]},{"name":"Greece","award":["HFRI-FM17-3648"],"award-info":[{"award-number":["HFRI-FM17-3648"]}]},{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation (H.F.R.I.)","doi-asserted-by":"publisher","award":["MIS-5000432"],"award-info":[{"award-number":["MIS-5000432"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation (H.F.R.I.)","doi-asserted-by":"publisher","award":["HFRI-FM17-3648"],"award-info":[{"award-number":["HFRI-FM17-3648"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Substantial evidence highlights divergences in immune responses between men and women. Women are more susceptible to autoimmunity, whereas men suffer from the more severe presentation of autoimmune disorders. The molecular mechanism of this sexual dimorphism remains elusive. Herein, we conducted a comprehensive analysis of sex differences in whole-blood gene expression focusing on alternative splicing (AS) events in systemic lupus erythematosus (SLE), which is a prototype sex-biased disease. This study included 79 SLE patients with active disease and 58 matched healthy controls who underwent whole-blood RNA sequencing. Sex differences in splicing events were widespread, existent in both SLE and a healthy state. However, we observed distinct gene sets and molecular pathways targeted by sex-dependent AS in SLE patients as compared to healthy subjects, as well as a notable sex dissimilarity in intron retention events. Sexually differential spliced genes specific to SLE patients were enriched for dynamic cellular processes including chromatin remodeling, stress and inflammatory responses. Remarkably, the extent of sexual differences in AS in the SLE patients and healthy individuals exceeded those in gene expression. Overall, this study reveals an unprecedent variation in sex-dependent splicing events in SLE and the healthy state, with potential implications for understanding the molecular basis of sexual dimorphism in autoimmunity.<\/jats:p>","DOI":"10.3390\/cells12232678","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T03:54:37Z","timestamp":1700625277000},"page":"2678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Extensive Alternative Splicing Patterns in Systemic Lupus Erythematosus Highlight Sexual Differences"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2289-3833","authenticated-orcid":false,"given":"Despoina","family":"Kosmara","sequence":"first","affiliation":[{"name":"Rheumatology and Clinical Immunology, University Hospital of Heraklion and University of Crete Medical School, 71500 Heraklion, Greece"},{"name":"Foundation for Research and Technology-Hellas (FORTH), Infections and Immunity, Institute of Molecular Biology and Biotechnology, 71110 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-1322","authenticated-orcid":false,"given":"Sofia","family":"Papanikolaou","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology, University Hospital of Heraklion and University of Crete Medical School, 71500 Heraklion, Greece"},{"name":"Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, Institute of Bioinnovation, 16672 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3001-6786","authenticated-orcid":false,"given":"Christoforos","family":"Nikolaou","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, Institute of Bioinnovation, 16672 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5299-1406","authenticated-orcid":false,"given":"George","family":"Bertsias","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology, University Hospital of Heraklion and University of Crete Medical School, 71500 Heraklion, Greece"},{"name":"Foundation for Research and Technology-Hellas (FORTH), Infections and Immunity, Institute of Molecular Biology and Biotechnology, 71110 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0140-6736(13)60954-X","article-title":"Immunopathogenic mechanisms of systemic autoimmune disease","volume":"382","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/ni0901-777","article-title":"Sex differences in autoimmune disease","volume":"2","author":"Whitacre","year":"2001","journal-title":"Nat. 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