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Browsing by Author "Lagström, Sonja"

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  • Savola, Paula; Kelkka, Tiina; Rajala, Hanna; Kuuliala, Antti; Kuuliala, Krista; Eldfors, Samuli; Ellonen, Pekka; Lagström, Sonja; Lepistö, Maija; Hannunen, Tiina; Andersson, Emma; Kumar Khajuria, Rajiv; Jaatinen, Taina; Koivuniemi, Riitta; Repo, Heikki; Saarela, Janna; Porkka, Kimmo; Leirisalo-Repo, Marjatta; Mustjoki, Satu (2017)
    Somatic mutations contribute to tumorigenesis. 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=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 (SLAMF6, IRF1) 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.