The functional aYnity of IgM rheumatoid factor is related to the disease duration in patients with rheumatoid arthritis

Objective—To determine the relevance of the functional aYnity of IgM rheumatoid factor (RF) to the clinical and serological characteristics of patients with rheumatoid arthritis. Methods—The functional aYnity of IgM RF of 57 seropositive rheumatoid arthritis patients was evaluated by an enzyme linked immunosorbent assay based on the use of a chaotropic agent. The inhibition index was taken as an estimate of functional aYnity. The patient group was divided into high functional aYnity subgroup 1 (functional aYnity < 0.5, n = 37) and low functional aYnity subgroup 2 (functional aYnity > 0.5, n = 20). The medical records of all patients were reviewed with a particular note of the disease activity and the articular damage score. Results—The disease duration was shorter (P < 0.01) in subgroup 1 patients [7.9 (SD 6.4) years] than in subgroup 2 patients [13.4 (11.29) years], so that Ritchie’s, Lee’s, and Steinbrocker’s indices were lower in the former than in the latter (P < 0.01, 0.001, and 0.01, respectively). In contrast, erythrocyte sedimentation rates, C reactive protein concentrations, antinuclear antibody, and HLA DR4 prevalences were similar in the two subgroups. Conclusions—DiVerent forms of RF are present during progression of the disease. (Ann Rheum Dis 1997;56:126–129) Rheumatoid factors (RF) are polyclonal antibodies that are directed against the Fc fragment of IgG. Rheumatoid arthritis is characterised by raised concentrations of RF. However, although RF are traditionally claimed to be found in rheumatoid arthritis, they are now widely acknowledged to be products of any ongoing normal immune response. It is not clear thus far whether there are distinct forms of RF, one pathological and another physiological. In vitro studies of aYnity suggest that RF of rheumatoid arthritis patients are diVerent of those of normal individuals. In vivo, the polyclonality of RF in rheumatoid arthritis makes it diYcult to characterise qualitative properties, such as specificity or avidity, which are likely to be important in determining their pathogenicity. However, earlier studies have developed a reproducible method for measuring the avidity index of RF. Therefore they estimated the avidity of RF in subjects with rheumatoid arthritis and controls. This has been termed “functional aYnity”. A higher functional aYnity of RF in the rheumatoid arthritis patients’ sera than in healthy controls has been described, suggesting the absence of a downregulating mechanism to limit the functional aYnity of RF in rheumatoid arthritis or an antigen driven response which would lead to antibody selection. Given the dearth of information regarding the functional aYnity of RF, the purpose of this study was to compare IgM RF from rheumatoid arthritis patients with high functional aYnity to those having low functional aYnity, and to address the issue as to whether extra-articular complications occur more frequently in patients with IgM RF of high functional aYnity compared with the remainder.