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.