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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Savola P,Kelkka T,Rajala HL,Kuuliala A,Kuuliala K,Eldfors S,Ellonen P,Lagström S,Lepistö M,Hannunen T,Andersson EI,Khajuria RK,Jaatinen T,Koivuniemi R,Repo H,Saarela J,Porkka K,Leirisalo-Repo M,Mustjoki S

doi

10.1038/ncomms15869

subject

Has Abstract

pub_date

2017-06-21 00:00:00

pages

15869

issn

2041-1723

pii

ncomms15869

journal_volume

8

pub_type

杂志文章

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