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


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Abstract

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.

About the authors

D. V. Shevyrev

Research Institute for Fundamental and Clinical Immunology

Author for correspondence.
Email: dr.daniil25@mail.ru
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

Email: vakoz40@yandex.ru
ORCID iD: 0000-0002-1756-1782
SPIN-code: 3573-7490

МD, PhD, Academician of the RAS

Russian Federation, Novosibirsk

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