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Reduction in experimental autoimmune thyroiditis by IgG Fc fragments bearing regRF epitopes

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Abstract

Previously, we identified a new immunoregulatory factor, the production of which provides rats with resistance to certain experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). RegRF inhibits the expansion of CD4 T lymphocytes by killing activated cells. CD4 T cells are essential for antibody production against a majority of antigens and for the generation of cytotoxic T cells; therefore, regRF is an attractive therapeutic biotarget for T-cell and antibody-mediated autoimmune diseases. RegRF is anti-idiotypic antibodies that have a shared paratope in addition to an individual paratope. Epitopes specific to the shared regRF paratope (regRF epitopes) can be obtained on conformers of IgG Fc fragments. Immunization with Fc fragments carrying regRF epitopes reduces rat collagen–induced arthritis and diminishes experimental autoimmune encephalomyelitis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune thyroiditis (EAT). Four weeks after EAT induction, rats were immunized with IgG Fc fragments exhibiting regRF epitopes. Histology studies of the thyroid were performed 4 weeks later. Thyroid function and other parameters were also evaluated. Treatment of rats with Fc fragments bearing regRF epitopes decreased the number of rats affected by EAT, significantly decreased the extent of thyroid damage, prevented thyroid metaplasia, and restored normal thyroid hormone production. Therefore, RegRF is a promising biotarget in autoimmune thyroiditis, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for that condition.

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Acknowledgements

The authors thank Jennifer Guernsey for editorial assistance.

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (project number 0827–2020-0012).

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Authors and Affiliations

  1. Department of Immunology and Cell Biology, Laboratory of Molecular and Cell Immunology, Udmurt State University, 1 Universitetskaya St, Izhevsk, 426034, Russian Federation

    Liubov Beduleva, Alexandr Sidorov, Alexey Terentiev, Kseniya Fomina & Igor Menshikov

  2. Laboratory of Biocompatible Materials, Udmurt Federal Research Center UB RAS, 34 T. Baramzinoy St, Izhevsk, 426067, Russian Federation

    Liubov Beduleva, Alexandr Sidorov, Alexey Terentiev, Viktor Varaksin, Kseniya Fomina & Igor Menshikov

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  1. Liubov Beduleva
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Conceptualization: LB. Investigation: LB, AS, AT, VV, KF. Writing—original draft: LB, AS. Writing—review and editing: IM.

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Correspondence to Liubov Beduleva.

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Beduleva, L., Sidorov, A., Terentiev, A. et al. Reduction in experimental autoimmune thyroiditis by IgG Fc fragments bearing regRF epitopes. Immunol Res 71, 83–91 (2023). https://doi.org/10.1007/s12026-022-09337-1

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