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Although these mutations occur in all proliferating cells, their accumulation under non-malignant conditions, such as in autoimmune disorders, has not been investigated. Here, we show that patients with newly diagnosed rheumatoid arthritis have expanded CD8+ T-cell clones; in 20% (5\/25) of patients CD8+ T cells, but not CD4+ T cells, harbour somatic mutations. In healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    =20), only one mutation is identified in the CD8+ T-cell pool. Mutations exist exclusively in the expanded CD8+ effector-memory subset, persist during follow-up, and are predicted to change protein functions. Some of the mutated genes (\n                    <jats:italic>SLAMF6, IRF1<\/jats:italic>\n                    ) have previously been associated with autoimmunity. RNA sequencing of mutation-harbouring cells shows signatures corresponding to cell proliferation. Our data provide evidence of accumulation of somatic mutations in expanded CD8+ T cells, which may have pathogenic significance for RA and other autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1038\/ncomms15869","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T05:49:23Z","timestamp":1498024163000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis"],"prefix":"10.1038","volume":"8","author":[{"given":"P.","family":"Savola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1085-6382","authenticated-orcid":false,"given":"T.","family":"Kelkka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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S.M. has received research funding from Ariad. J.S. has received lecture fees from Roche. The remaining authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15869"}}