Specificity of the reaction between rheumatoid factors and gamma globulin

Rheumatoid factors in the sera of patients with rheumatoid arthritis appear to be specifically directed against genetically determined "antigens" in human gamma-globulin. At least eight rheumatoid factors of differing specificity exist; usually several are present in combination in the same serum. The different rheumatoid factors can be readily detected through their pattern of reactivity with anti-Rh antibodies from different individuals. Rheumatoid factors in diseases other than rheumatoid arthritis were found to have a more restricted specificity, contrasted to the broader reactivity of the factors in most rheumatoid arthritis sera. A specificity similar to that for incomplete antibodies was not demonstrated for the reaction of rheumatoid factors with aggregated gamma-globulin or with gamma-globulin to form the "22S complex." In certain instances, using the anti-Rh system, rheumatoid factors were found to react poorly with the patient's own gamma-globulin, compared to that of other individuals of different genetic gamma-globulin types. These results, as well as additional indirect evidence, indicate that the rheumatoid factors can possess isospecificity. However, a certain degree of autospecificity was also found which was most clearly evident through complex formation with the patients own gamma-globulin and in the reaction with aggregates. The relevance of these findings to possible isoantibody as well as autoantibody concepts is discussed.