Immobilized Reagents For Removal Of Circulating Immune Reactants In Vivo
The role of immune reactants in many experimental and human diseases is now well established, Cochrane C. C., Koffler D.: Immune complex disease in experimental animals and man. Advances Immunol 16:185-233, 1973; Wilson C. B., Border W. A., Lenham D. H.: Renal diseases in Basic and Clinical Immunology. (Fudenberg, HH, ed.). Lange Publications, Los Altos, Calif., 1976, pg. 562. Therapy for many of these immunologically mediated diseases has consisted largely of the use of pharmacological agents that widely and non-specifically suppress host immunity leading to numerous undesirable effects. With increasing awareness of the etiopathogenic factors in many autoimmune diseases many sensitive radioimmunological techniques to measure them in serum. Various immunoadsorbents designed to extract pathogenic immune reactants from the circulation have been developed. For example, immunoadsorbents consisting of immobilized antigens, antibodies and enzymes have been developed. When placed in an extracorporeal circuit, these immunoadsorbents have shown a capacity to extract or hydrolyze immune reactants in the circulation without demonstrable release of immobilized substances or significant immediate or long-range toxicity to the host.
Graf et al, Graff M. W., Uhr J. W.: Regulation of antibody formation by serum antibody. I. Removal of specific antibody by means of immunoadsorption. J Exp Med 50:130-1175, 1969, were the first to show that immunoadsorbents could be employed to selectively remove antibodies from actively and passively immunized rabbits. In later studies, Schenkein et al., Schenkein I., Brystryn J. C., Uhr, J. W.: Specific removal of in vivo antibody by extracorporeal circulation over an immunoadsorbent in gel. J Clin Invest 50:1864-1870, 1971, developed an extracorporeal immunoadsorbent system in which bovine serum albumin (BSA) was immobilized in agarose and proved capable of selectively removing BSA antibodies from the circulation. A similar immunoadsorbent in which ssDNA antigen was immobilized and proved capable of extracting ssDNA antibody in both passively and actively immunized rabbits, Terman D. S., Stewart I., Robinette J., Carr R., Harbeck R.: Specific removal of DNA antibodies in vivo with an extracorporeal immunoadsorbent. Clinical and Experimental Immunology 24:231-238, 1976. Because of the fragility of the supporting matrix and the possibility of leaching of immobilized substances, new and more stable extracorporeal immunoadsorbents were subsequently developed.
Various antigens such as bovine serum albumin (BSA), deoxyribonucleic acid (DNA), glomerular basement membrane (GBM) extract have been immobilized on several solid supports and these have been employed as extracorporeal immunoadsorbents, Terman D. S., Durante D., Buffaloe G., McIntosh R.: Attenuation of canine nephrotoxic glomerulonephritis with an extracorporeal immunoadsorbent. Scandinavian Journal of Immunology 6, 1977: Terman D. S., Petty D., Ogden D., Harbeck R., Buffaloe G., Carr R.: Specific removal of DNA antibodies in vivo by extracorporeal circulation over DNA immobilized in collodion-charcoal. Clinical Immunology and Immunopathology 8, 1977; Terman D. S., Tavel T., Petty D., Racic M. R., Buffaloe G.: Specific removal of antibody by extracorporeal circulation over antigen immobilized in collodion-charcoal. Clinical and Experimental Immunology 28, 1977; Terman D. S., Tavel T., Petty D., Tavel A., Harbeck R., Buffaloe G., Carr R.: Specific removal of bovine serum albumin (BSA) antibodies by extracorporeal circulation over BSA immobilized in nylon microcapsules. Terman et al, Journal of Immunology 116:1337, 1976; Terman D. S., Stewart I., Robinett J., Carr R., Harbeck, R.: Specific removal of DNA antibodies in vivo with an extracorporeal immunoadsorbent. Terman et al, Clin Exp Immunol 24:231, 1976.
Circulating immune complexes have now been implicated in the pathogenesis of numerous diseases. Their presence in the circulation often correlates with disease activity and they may be found deposited in tissues, Zubler R. H., Lambert P. H.: Detection of immune complexes in human diseases. Prog Allergy 24:1, 1978. In addition to studies described above for hydrolysis of nDNA:antiDNA complexes, preliminary work has shown that Clq, the first component of complement, may be immobilized in collodion membranes and will bind to immune complexes circulated over them. Terman et al FEBS, Letters, 68, 89, 1976.