The role of homeostatic proliferation and SNP mutations in MHC genes in the development of rheumatoid arthritis

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Great efforts have been made to study the etiology and pathogenesis of rheumatoid arthritis in the last few decades, but this issue remains widely unknown. In this review, we suggest a hypothesis according to which the development of rheumatoid arthritis is associated with a genetically determined enhancement of self-antigens presentation and decrease in TCR repertoire diversity due to homeostatic proliferation (HP). We suppose that qualitative changes in the TCR landscape of effector and regulatory T-cells populations lead to immune disequilibrium. I.e. HP results in the condition when self-reactive T-cell clones appear to which no specific T-regulatory cells exist. If such self-reactive clones have TCR specific to modified auto-antigens, which presentation increased due to SNP mutations in MHC genes, then the adaptive immunity is activated, and rheumatoid arthritis develops. Obviously, therapy based on the deletion of self-reactive T-cells clones involved in the RA process or on the replenishment of Treg clones by CAR-T-cells is the perspective approach of personalized medicine.

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About the authors

D. V. Shevyrev

Research Institute for Fundamental and Clinical Immunology

Author for correspondence.
ORCID iD: 0000-0002-7084-081X
SPIN-code: 2327-7486

MD, PhD, Junior Research Associate

Russian Federation, Novosibirsk

V. A. Kozlov

Research Institute for Fundamental and Clinical Immunology

ORCID iD: 0000-0002-1756-1782
SPIN-code: 3573-7490

МD, PhD, Academician of the RAS

Russian Federation, Novosibirsk


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