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

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http://hdl.handle.net/10138/212620

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Savola , P , Kelkka , T , Rajala , H L , Kuuliala , A , Kuuliala , K , Eldfors , S , Ellonen , P , Lagstrom , S , Lepisto , M , Hannunen , T , Andersson , E I , Khajuria , R K , Jaatinen , T , Koivuniemi , R , Repo , H , Saarela , J , Porkka , K , Leirisalo-Repo , M & Mustjoki , S 2017 , ' Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis ' , Nature Communications , vol. 8 , 15869 . https://doi.org/10.1038/ncomms15869

Title: Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis
Author: Savola, P.; Kelkka, T.; Rajala, H. L.; Kuuliala, A.; Kuuliala, K.; Eldfors, S.; Ellonen, P.; Lagstrom, S.; Lepisto, M.; Hannunen, T.; Andersson, E. I.; Khajuria, R. K.; Jaatinen, T.; Koivuniemi, R.; Repo, H.; Saarela, J.; Porkka, K.; Leirisalo-Repo, M.; Mustjoki, S.
Contributor organization: Medicum
Department of Clinical Chemistry and Hematology
Clinicum
Department of Oncology
Hematologian yksikkö
University of Helsinki
Department of Bacteriology and Immunology
Institute for Molecular Medicine Finland
Reumatologian yksikkö
Department of Medicine
Janna Saarela / Principal Investigator
HUS Comprehensive Cancer Center
HUS Inflammation Center
HUS Internal Medicine and Rehabilitation
Date: 2017-06-21
Language: eng
Number of pages: 14
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/ncomms15869
URI: http://hdl.handle.net/10138/212620
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.
Subject: PROTEIN FUNCTION
CELL REPERTOIRE
ELDERLY INDIVIDUALS
STAT3 MUTATIONS
INNATE IMMUNITY
HEMATOPOIESIS
BLOOD
EXPANSIONS
LEUKEMIA
CANCER
3122 Cancers
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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