Suppression of experimental autoimmune encephalomyelitis by IgG Fc fragments bearing regRF epitopes.

Abstract

Previously we identified a rheumatoid factor, the production of which provides rats with resistance to experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). Immunization with conformers of IgG Fc fragments carrying epitopes specific to regRF reduces rat collagen-induced arthritis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune encephalomyelitis, and to evaluate the potential of a strategy of stimulating production of regRF to treat multiple sclerosis. Two days after myelin basic protein injection, rats were immunized with Fc fragments exhibiting regRF epitopes, as well as with Fc fragments without those epitopes. The effect of Fc immunization on clinical signs of EAE and immunological parameters was evaluated. Stimulation of regRF production by IgG Fc fragments bearing regRF epitopes diminished EAE symptoms in rats, while immunization with Fc fragments without those epitopes worsened EAE. The improvement of EAE symptoms in rats treated with Fc fragments bearing regRF epitopes was associated with regRF production and with the relatively low number of blood CD4 T lymphocytes during disease development. In experiments involving immunizing intact rats and lymph node mononuclear cell cultures, Fc fragments bearing regRF epitopes decreased the CD4 T lymphocyte population indirectly, via regRF production. RegRF is a promising biotarget in MS, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for MS.

• Authors: Liubov Beduleva, Tatyana Khramova, Alexandr Sidorov, Alexey Terentiev, Nadezhda Abisheva, Daria Menshikova, Pavel Ivanov, Kseniya Fomina, Anna Gorbushina, Natalia Shklyaeva, Igor Menshikov
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 101 Issue Pt A Pg. 108309 (Dec 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 34731688 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Epitopes
• Immunoglobulin Fc Fragments
• Immunoglobulin G
• Rheumatoid Factor

Topics

• Animals
• CD4 Lymphocyte Count
• Encephalomyelitis, Autoimmune, Experimental (immunology, therapy)
• Enzyme-Linked Immunosorbent Assay
• Epitopes (immunology)
• Immunoglobulin Fc Fragments (immunology, therapeutic use)
• Immunoglobulin G (immunology, therapeutic use)
• Lymph Nodes (immunology)
• Lymphocytes (immunology)
• Male
• Rats
• Rats, Wistar
• Rheumatoid Factor (immunology)