Immune complexes and the rheumatic diseases

There is good evidence that immune complexes occur frequently during some major rheumatic diseases, especially SLE and rheumatoid arthritis. This evidence is based on the demonstration of immune complexes in blood, in various extravascular fluids and in some tissue structures. The presence of soluble immune complexes has been suspected from physicochemical analysis of serum and synovial fluid, and from the recognition of biological effects largely specific for such immune reactants. The recent development of methods allowing for a quantitation of immune complexes based on some of their biological reactivities, provides a new approach for the investigation of the pathogenesis of rheumatic diseases. In view of the data presently available, it appears that immune complexes may occur in a large number of pathological conditions and that their pathogenicity may be expressed at various degrees. Obviously, the biological activities of these naturally occurring immune complexes differ according to the clinical situation and this heterogeneity is responsible for the various types of reactivity observed in the biological assays used for the detection of immune complexes. Although it is generally considered that circulating immune complexes play an essential role in the development of vascular and glomerular lesions associated with rheumatic diseases, we think that the existence of a large extravascular pool of soluble and insoluble immune complexes should be considered in relation to the frequent occurrence of inflammatory lesions in the extravascular compartment. The possible pathogenic role of immune complexes formed in the extravascular spaces is particularly demonstrated in pleural or articular localization of SLE and rheumatoid arthritis. For example, it is clear that immune complexes are present in synovial fluid from patients with rheumatoid arthritis in higher concentrations than in serum, and that their particular physicochemical characteristics are expressed in a particularly efficient biological activity. It is unlikely that such complexes would be the result of a simple diffusion of circulating immune complexes into the synovium. The persistence and the pathogenicity of immune complexes directly formed in the extravascular compartment are certainly favoured by the limited clearance capacity of the mononuclear-phagocytic system in this compartment as compared to the efficient clearance mechanism operating in the circulation and particularly during passage through the liver and spleen. The clinical relevance of the detection of immune complexes and of the evaluation of their effect on the complement system has been particularly demonstrated in SLE and in rheumatoid arthritis. Such parameters appear useful for the diagnosis, follow-up during therapy, and understanding of the pathogenesis of clinical manifestations. One can hope that the present efforts to isolate and identify the components of the immune complexes will also provide information relevant to the aetiology of some of the rheumatic diseases.