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THE CLINICAL SIGNIFICANCE OF IMMUNE COMPLEXES IN RHEUMATOID DISEASE *

In recent years, immune complexes have been implicated in the pathogenesis of several human diseases. The main support for their pathogenic role has been obtained from studies of experimental serum sickness and of many naturally occurring diseases of animals. In 1968, Baumal and Broder described a factor that resembled a soluble immune complex and was detected in rheumatoid serum and synovial fluid by its capacity to release histamine from the perfused guinea pig lung.' For this reason, it was called the rheumatoid biologically active factor (RBAF) . The RBAF has the properties of a soluble antigen-antibody complex and has been found in one third of rheumatoid sera and in two thirds of rheumatoid synovial fluids but not in healthy persons. It is macromolecular by SephadexB G-200 chromatography and ultracentrifugation. It contains IgG but not IgM or IgA, and it fixes complement but is not rheumatoid factor and is not cryoprecipitable or an intermediate complex. The RBAF is labile to brief exposure at pH 3 or heat at 56" C and is eluted from DEAE-cellulose at higher molarity than is IgG. These properties indicate that the RBAF resembles a soluble immune complex that contains IgG and a second constituent not yet identified.2 In 1965, a prospective study was initiated at the Wellesley Hospital in Toronto to assess the significance of the RBAF in 127 patients with definite or classic rheumatoid arthritis. This report describes the results of serial assessments on these patients since that time, All clinical evaluations were performed with a uniform protocol by clinicians who did not know whether the patient's serum or synovial fluid contained the RBAF. There were 127 patients assessed initially, and 9 months later, 107 of them were again evaluated. Forty-six months later, a third assessment was conducted on 86 patients (TABLE 1 ) . The sex distribution of cases at each evaluation was approximately the same. The mean age and duration of disease increased over the course of the study. The functional class of patients, mean grip strength, number of synovial effusions, and the frequency with which patients were taking corticosteroids were approximately the same at each assessment. However, the frequency of extraarticular features was greater at the first and second assess-