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

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.

Comparison of the specificity of rheumatoid factor detected by latex fixation with that of regulatory rheumatoid factor.

BACKGROUND: Rheumatoid factor (RF), originally defined as pathological autoantibodies to IgG that are detected in rheumatoid arthritis, turned out to be multi-specific antibodies, some of which exhibit immunoregulatory properties. Recently, we identified a RF, the production of which confers resistance to experimental autoimmune diseases and is associated with the remission of autoimmune diseases. To differentiate the RF, we discovered from the one associated with rheumatic disease onset or progression and to reflect its immunoregulatory properties, we named it regulatory rheumatoid factor (regRF). Immunization with conformers of Fc fragments that expose regRF neoepitopes reduces collagen-induced arthritis in rats. Certain information about the specificity of classical RF and regRF indicates that these populations may be one and the same. Therefore, the aim of this study was to determine whether there is a difference between the classical RF and regRF. METHODS: Classical RF was measured in diseased blood by the latex fixation method, and regRF was detected by the agglutination of human IgG-loaded tanned erythrocytes. Competitive analysis was used to determine the specificity of rheumatoid factors. RESULTS: It was found that regRF and pathology-associated RF constitute different antibody populations. Pathology-associated RF is specific for lyophilized IgG. RegRF does not interact with IgG. RegRF is specific to conformers of IgG Fc fragments that have a reduced hinge. In latex-positive rheumatoid arthritis sera, regRF may be present in addition to pathology-associated RF. The latex fixation method detects both rheumatoid factor populations. CONCLUSION: RegRF and classical pathology-associated RF have different specificity.