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Nat Commun. 2017 Jun 21;8:15869. doi: 10.1038/ncomms15869.

Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis.

Author information

1
Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Centre, Haartmaninkatu 8, FIN-00290 Helsinki, Finland.
2
Department of Clinical Chemistry and Hematology, University of Helsinki, Haartmaninkatu 8, FIN-00290 Helsinki, Finland.
3
Bacteriology and Immunology, Medicum, University of Helsinki, Haartmaninkatu 3, FIN-00290 Helsinki, Finland.
4
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, FIN-00290 Helsinki, Finland.
5
Histocompatibility Testing Laboratory, Finnish Red Cross Blood Service, Kivihaantie 7, FIN-00310 Helsinki, Finland.
6
Department of Rheumatology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.

Abstract

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.

PMID:
28635960
PMCID:
PMC5482061
DOI:
10.1038/ncomms15869
[Indexed for MEDLINE]
Free PMC Article

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