Frequent somatic mosaicism in T lymphocyte subsets in individuals with and without multiple sclerosis.

Autor:	Van Horebeek L; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, Katholieke Universiteit (KU) Leuven, Leuven, Belgium., Dedoncker N; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, Katholieke Universiteit (KU) Leuven, Leuven, Belgium., Dubois B; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.; Department of Neurology, University Hospitals Leuven, Leuven, Belgium., Goris A; Laboratory for Neuroimmunology, Department of Neurosciences, Leuven Brain Institute, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Dec 23; Vol. 13, pp. 993178. Date of Electronic Publication: 2022 Dec 23 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.993178
Abstrakt:	Background: Somatic variants are variations in an individual's genome acquired after the zygotic stadium and result from mitotic errors or not (fully) repaired DNA damage. Objectives: To investigate whether somatic mosaicism in T lymphocyte subsets is enriched early in multiple sclerosis (MS). Methods: We identified somatic variants with variant allele fractions ≥1% across the whole exome in CD4 + and CD8 + T lymphocytes of 21 treatment-naive MS patients with <5 years of disease duration and 16 partially age-matched healthy controls. We investigated the known somatic STAT3 variant p.Y640F in peripheral blood in a larger cohort of 446 MS patients and 259 controls. Results: All subjects carried 1-142 variants in CD4 + or CD8 + T lymphocytes. Variants were more common, more abundant, and increased with age in CD8 + T lymphocytes. Somatic variants were common in the genes DNMT3A and especially STAT3 . Overall, the presence or abundance of somatic variants, including the STAT3 p.Y640F variant, did not differ between MS patients and controls. Conclusions: Somatic variation in T lymphocyte subsets is widespread in both control individuals and MS patients. Somatic mosaicism in T lymphocyte subsets is not enriched in early MS and thus unlikely to contribute to MS risk, but future research needs to address whether a subset of variants influences disease susceptibility. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Van Horebeek, Dedoncker, Dubois and Goris.)
Databáze:	MEDLINE
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