Regulatory and other rheumatoid factors in rheumatoid arthritis patients with active disease or in remission.

BACKGROUND: Previously, we identified a regulatory rheumatoid factor (regRF), the production of which provides rats with resistance to collagen-induced arthritis (CIA). Immunization with conformers of IgG Fc fragments carrying epitopes specific to regRF reduces symptoms of CIA. The aim of this study was to determine whether there is a link between regRF levels and rheumatoid arthritis (RA) activity in humans in order to assess the potential of regRF as a therapeutic biotarget in RA. The variability of rheumatoid factor (RF) specificities present in the blood of RA patients was also studied. METHODS: The regRF were studied in RA patients with active disease and in remission. Variability in the specificities of RF associated with RA was studied by concurrent inhibition of RF latex fixation by variants of modified IgG. RESULTS: Patients in remission had regRF levels higher than in healthy subjects. The regRF in remission was characterized by tight binding to its antigen, as in healthy subjects. The regRF levels in patients with active RA varied dramatically, and regRF binding to its antigen was weak. The exacerbation of Still's disease coincided with low regRF levels and affinity, while an improvement in patient condition was associated with an increase in regRF levels and affinity. The RF specific to RA, which was detected by the RF latex-fixation method, was a nonhomogeneous population of antibodies that included RF to lyophilized IgG, to IgG immobilized on polystyrene, and to rabbit IgG. CONCLUSION: Stimulating regRF production might enable improved RA therapy.

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.