Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15869
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Funding
- European Research Council (M-IMM project)
- Academy of Finland
- Finnish special governmental subsidy for health sciences, research and training
- Sigrid Juselius Foundation
- Instrumentarium Science foundation
- Finnish Cultural Foundation
- Maire Lisko foundation
- Emil Aaltonen foundation
- Orion research foundation
- Finnish Cancer Institute
- Cancer Foundation Finland sr [120107, 140142, 130127] Funding Source: researchfish
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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.
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