Heberden Oration, 1964 : Some Immunologic Aspects of the Connective Tissue Diseases

Abstract

Lesions observed in the joints and heart appear to be the result of a reaction between foreign cell and host antigen; but the possibility that they are a consequence of a hypersensitivity reaction to an infectious agent remains to be considered. The synovial membrane with its layer of phagocytic lining cells may be potentially capable of functioning as a site of primary immunization, leading to infiltration of its deeper layers with mononuclear cells as a consequence of uptake of antigen from the synovial space. In the presence of established hypersensitivity, it could also be the site of proliferation of sensitized cells. In these respects, the synovial membrane would have features in common with a lymph node; and, like the lymph node, it could be maintained in a chronically active state in a localized anatomical site by the continuous availability of antigen to that site. Evidence of direct interaction between synovial cells and lymphocytes in the rheumatoid synovial membrane has not been observed in electron microscopic studies. Available information suggests the existence of an antigen in the synovial fluid or in contact with it. This antigen may be an autologous constituent, but it is not possible to rule out a latent infectious agent in this role. Autoantibody formation in rheumatoid arthritis tends to be stalled, at least in part, at the level of the primary or 19S response. This is not inconsistent with the histological character of the rheumatoid inflammatory process and its tendency to remain localized. In contrast, the patient with SLE tends to produce a number of serum autoantibodies; these appear to be present in relatively high titer and to undergo a relatively marked transition to the 7S form. The clinical and serological features of SLE are, furthermore, consistent with the presence of increased amounts of 7S autoantibody in the blood. Differences in serum autoantibody formation between rheumatoid arthritis and systemic lupus erythematosus, it is suggested, represent a variation in host response.