Studies on Circulating Immune Complexes

Abstract

With the observations of immune complexes or antigens in the circulation of patients with rheumatoid arthritis (1, 2), systemic lupus erythematosus (3, 4), and other diseases, much attention has been drawn to their possible significance in the pathogenesis of the lesions in these disorders. Abundant data derived from experimental models have shown that the presence of complexes in the circulation coincides temporally with the development of the lesions, e.g., acute glomerulonephritis and vasculitis (5, 6) and chronic glomerulonephritis (7). In these studies the complexes were demonstrable in the lesions, and it was reasonably presumed that they reached their destination in the tissues after passage through the circulation.Previous studies in this series have analyzed the mechanisms by which circulating immune complexes are capable of localizing in vessel walls. It was found that complexes localized in blood vessd walls only during an increase in vascular permeability and that the complexes were trapped along the vascular basement membranes during the passage of plasma fluids through the permeable membrane (8). The increase of vascular permeability was brought about in particular by vasoactive amines and histamine that were released from their tissue reservoirs, the mast cells, by the action of the complexes themselves (9). The accompanying article presents data suggesting that this mechanism of localization is instrumental in serum sickness.The present paper deals with the physicochemical properties of complexes and with the concentration of complexes in the plasma required for detectable localization to occur. The validity of these findings is tested in experimental serum sickness of rabbits, a disease known to be caused by deposition of circulating immune complexes. A preliminary report has been presented (10).

Leukocyte-Dependent Histamine Release From Rabbit Platelets

“…This deposition was not inhibited by depletion of circulating complement (10,27) and a good correlation was observed between the presence of LDHR and induction of glomerulonephritis (i0). Many observations have linked vasopermeability induced by vasoactive amine release and deposition of immune complexes and other macromolecules in blood vessels (28)(29)(30)(31)(32)(33)(34) or even worm expulsion through intestinal mucosae in parasitic infections of rats (35). This suggests that anaphylactic reactions might be involved not only in allergic diseases but might also play a physiologic role in defense mechanisms; they could initiate heightened passage of molecules of different sizes and even cells through vessel walls, glomeruii, and mucosae.…”

Circulating Immune Complexes in Lyme Arthritis

“…Although precise identification of this material will require its isolation, dissociation, and specific reassembly, the fact that it is of high molecular weight, contains IgG, and reacts with Clq suggests that it represents antigen-antibody complexes. Immune complexes of this size are likely to initiate tissue injury (27), and it may be important that the largest amounts of this material were found in patients with severe clinical manifestations. The high density material was detected best in the assays based on Clq binding; thus, it is not surprising that sera from patients with active disease were more frequently positive in the 1251-Clq binding and the Clq solid phase assays than in the Raji cell assay.…”

Reduction of Phagocyte Adherence by Nephritic Sera: Relation to Complement Activation

“…Systemic complement activation, such iIS occurs with immune complex diseases, appears to paralyze phagocytes (I 5). Unable to adhere to the glomerular capillary endothelium and phagocytose immune complexes lodged there, phagocytes may damage the glomerular basement membrane with lysosomal enzymes (14,15) released in response to locally deposited complement by-products (6,35). Alternately, the observed impaired phagocyte adherence might be related to leukocyte aggregation which may also occur in association with systemic complement activation (1 6).…”