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High\u2010throughput sequencing of the T cell receptor (TR) offers several applications beyond diagnostic purposes, including the study of T cell pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed high\u2010throughput RNA sequencing of the TR alpha (TRA) and beta (TRB) genes focusing on the complementarity\u2010determining region 3 (CDR3) in 11 SS and one erythrodermic mycosis fungoides (MF) patients. Five psoriasis patients were employed as controls. Peripheral blood CD4<jats:sup>+<\/jats:sup> cells were isolated and RNA sequenced (HiSeq2500). High\u2010resolution HLA typing was performed in neoplastic patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Highly expanded predominant TRA and TRB CDR3 were only found in SS patients (median frequency: 94.4% and 93.7%). No remarkable CDR3 expansions were observed in psoriasis patients (median frequency of predominant TRA and TRB CDR3: 0.87% and 0.69%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 compared to SS). CDR3 almost identical to the predominant were identified within each SS patient and were exponentially correlated with frequencies of the predominant CDR3 (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.918, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Forty\u2010six different CDR3 were shared between SS patients displaying HLA similarities, including predominant TRA and TRB CDR3 in one patient that were found in other three patients. Additionally, 351 antigen matches were detected (Cytomegalovirus, Epstein\u2013Barr, Influenza virus, and self\u2010antigens), and the predominant CDR3 of two different SS patients matched CDR3 with specificity for Influenza and Epstein\u2013Barr viruses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Besides detecting clonality, these findings shed light on the nature of SS\u2010related antigens, pointing to RNA sequencing as a useful tool for simultaneous clonality and biological analysis in SS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24982","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T07:10:29Z","timestamp":1703056229000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High\u2010throughput RNA sequencing of the T cell receptor alpha and beta chains for simultaneous clonality and biological analyses in Sezary syndrome"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-3764","authenticated-orcid":false,"given":"Gonzalo","family":"Blanco","sequence":"first","affiliation":[{"name":"Grup de Recerca Translacional en Neopl\u00e0sies Hematol\u00f2giques, Cancer Research Programme IMIM\u2010Hospital del Mar  Barcelona Spain"},{"name":"Laboratori de Citogen\u00e8tica Molecular, Servei de Patologia Hospital del Mar  Barcelona Spain"},{"name":"Karches Center for Oncology Research The Feinstein Institutes for Medical Research, Northwell Health  Manhasset New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5097-5621","authenticated-orcid":false,"given":"Daniel","family":"L\u00f3pez\u2010Avent\u00edn","sequence":"additional","affiliation":[{"name":"Servei de Dermatologia Hospital del Mar  Barcelona Spain"},{"name":"Programa de Doctorat en Medicina, Departament de Medicina Universitat Aut\u00f2noma de Barcelona (UAB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-6055","authenticated-orcid":false,"given":"Ramon M.","family":"Pujol","sequence":"additional","affiliation":[{"name":"Servei de Dermatologia Hospital del Mar  Barcelona Spain"},{"name":"Grup de Recerca en Malalties Inflamat\u00f2ries i Neopl\u00e0siques Dermatol\u00f2giques, Inflammation and Cardiovascular Disorders Research Programme IMIM\u2010Hospital del Mar  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-6730","authenticated-orcid":false,"given":"Andrea","family":"G\u00f3mez\u2010Llon\u00edn","sequence":"additional","affiliation":[{"name":"Grup de Recerca Translacional en Neopl\u00e0sies Hematol\u00f2giques, Cancer Research Programme IMIM\u2010Hospital del Mar  Barcelona Spain"},{"name":"Laboratori de Citogen\u00e8tica Molecular, Servei de Patologia Hospital del Mar  Barcelona 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