Regulatory rheumatoid factor in rat model of Sjogren’s syndrome

Cover Page

Cite item

Full Text

Abstract

Earlier, we have revealed a novel factor regulating autoreactivity called regulatory rheumatoid factor (regRF), which is represented by a population of anti-idiotypic antibodies that have a common paratope specific to the PD1 molecule. RegRF exerts cytotoxic effect on activated PD-1+CD4 T lymphocytes and controls the lymphocyte expansion. Its production during the induction period prevents experimental autoimmune diseases in rats. The association between regRF and resistance to these disorders suggests that regRF stimulation may be an effective treatment of autoimmune diseases. Sjögren’s syndrome (SS) is an autoimmune disease that may accompany other autoimmune diseases or occur independently. Salivary gland (SG) lesions and lymphocytopenia may develop in SS. It is not known whether the regRF is a resistance factor to SS, and if the regRF stimulation may be used to treat this condition. The aim of this study was to clarify the role of regRF in ensuring resistance to Sjogrens syndrome in rats. SS was induced in Wistar rats by immunization with proteins isolated from murine SG. Blood samples were taken from the caudal vein each week before and after the immunization. Histological analysis of submandibular SG tissue was performed 12 weeks after the initial immunization. Autoantibodies to CD4 were detected in serum by ELISA; regRF levels were measured by agglutination of IgG-coated erythrocytes; CD3+, CD4+ and CD8+ lymphocyte counts were determined by flow cytometry in blood samples. 40% of rats immunized with mouse SG proteins, have developed SG lesions typical of sialoadenitis occurring in Sjogren’s syndrome. 50% of rats exhibited chronic lymphocytopenia (CD3, CD4 and CD8 cell populations) in response to immunization with mouse SG proteins. In rats with CD4 lymphocytopenia, no autoantibodies to CD4 have been found. An association has been found between a high level of regRF on day 7 following immunization with mouse SG proteins and resistance to sialadenitis in rats. However, lymphocytopenia did not depend on regRF production during induction of SS. Thus, regulatory rheumatoid factor is a preventive factor for sialoadenitis, but not to lymphocytopenia in rat model of Sjogren’s syndrome.

About the authors

Pavel V. Ivanov

Udmurt State University

Author for correspondence.
Email: aka.ven1k@gmail.com

PhD (Biology), Senior Researcher, Laboratory of Molecular and Cell Immunology

Russian Federation, Izhevsk, Udmurt Republic

A. Yu. Sidorov

Udmurt State University; Udmurt Federal Research Center, Ural Branch, Russian Academy of Sciences

Email: aka.ven1k@gmail.com

PhD (Biology), Senior Researcher, Laboratory of Molecular and Cell Immunology, Senior Researcher, Laboratory of Biocompatible Materials

Russian Federation, Izhevsk, Udmurt Republic

A. S. Terentiev

Udmurt State University; Udmurt Federal Research Center, Ural Branch, Russian Academy of Sciences

Email: aka.ven1k@gmail.com

Senior Researcher, Laboratory of Molecular and Cell Immunology, Researcher, Laboratory of Biocompatible Materials

Russian Federation, Izhevsk, Udmurt Republic

I. S. Cherepanov

Udmurt State University

Email: aka.ven1k@gmail.com

PhD (Chemistry), Associate Professor, Department of Fundamental and Applied Chemistry

Russian Federation, Izhevsk, Udmurt Republic

References

  1. Beduleva L., Menshikov I., Stolyarova E., Fomina K., Lobanova O., Ivanov P., Terentiev A. Rheumatoid factor in idiotypic regulation of autoimmunity. Int. J. Rheum. Dis., 2015, Vol. 18, no. 4, pp. 408-420.
  2. Khramova T., Beduleva L., Sidorov A., Terentiev A., Menshikov I. Regulatory rheumatoid factor is specific to PD-1 and Uses PD-1 pathway to control CD4 T lymphocytes. Immunol. Invest., 2023, Vol. 52, no. 7, pp. 897-908.
  3. Liao R., Yang H.T., Li H., Liu L.X., Li K., Li J.J., Liang J., Hong X.P., Chen Y.L., Liu D.Z. Recent advances of salivary gland biopsy in Sjögren’s Syndrome. Front. Med. (Lausanne), 2022, Vol. 8, 792593. doi: 10.3389/fmed.2021.792593.
  4. Negrini S., Emmi G., Greco M., Borro M., Sardanelli F., Murdaca G., Indiveri F., Puppo F. Sjögren’s syndrome: a systemic autoimmune disease. Clin. Exp. Med., 2022, Vol. 22, no. 1, pp. 9-25.
  5. Patel R., Shahane A. The epidemiology of Sjögren’s syndrome. Clin. Epidemiol., 2014, Vol. 6, pp. 247-255.
  6. Sidorov A., Beduleva L., Menshikov I., Terentiev A., Stolyarova E., Abisheva N. Fc fragments of immunoglobulin G are an inductor of regulatory rheumatoid factor and a promising therapeutic agent for rheumatic diseases. Int. J. Biol. Macromol., 2017, Vol. 95, pp. 938-945.
  7. Stolyarova E., Beduleva L., Menshikov I., Snigiryev A., Khramova T. Mechanism by which regulatory rheumatoid factor prevents experimental autoimmune encephalomyelitis. Endocr. Metab. Immune Disord. Drug Targets, 2018, Vol. 18, no. 6, pp. 596-601.
  8. Sudzius G., Mieliauskaite D., Siaurys A., Viliene R., Butrimiene I., Characiejus D., Dumalakiene I. Distribution of Peripheral Lymphocyte Populations in Primary Sjögren’s Syndrome Patients. J. Immunol. Res., 2015, Vol. 2015, 854706. doi: 10.1155/2015/854706.
  9. Yura Y., Hamada M. Outline of salivary gland pathogenesis of Sjögren’s Syndrome and current therapeutic approaches. Int. J. Mol. Sci., 2023, Vol. 24, no. 13, 11179. doi: 10.1371/10.3390/ijms241311179.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Figure 1. A, B, sections of the submandibular salivary glands of rats immunized with heterologous homogenate of mouse salivary glands. A, rats with histopathological changes similar to Sjogren’s syndrome B, rats without changes. Coloring, N&E. *, sites of destruction of the epithelium of granular ducts. Arrows, foci of hyperplasia. C, kinetics of regulatory rheumatoid factor in rats with changes in salivary glands sensitive to the development of Sjogren’s syndrome and rats without changes in salivary glands resistant to the development of Sjogren’s syndrome. Note. Each point is represented as the average ± SD. *, p < 0.05, Mann–Whitney criterion.

Download (2MB)
3. Figure 2. The number of CD3 T lymphocytes (A), CD8 T lymphocytes (B) and CD4 T lymphocytes (C) in the blood of rats immunized with mouse salivary gland homogenate. Kinetics of CD4 autoantibodies in rats with and without CD4 T-lymphocytopenia (B). Kinetics of regulatory rheumatoid factor in rats with and without lymphocytopenia (D) Note. Each point is represented as the mean ± SD.

Download (546KB)

Copyright (c) 2025 Ivanov P.V., Sidorov A.Y., Terentiev A.S., Cherepanov I.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).