Isolation and Characterization of Antibodies and other Immunologically Reactive Substances from Rejecting Renal Allografts

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Abstract
Summary: Tissue bound, complement fixing (and presumably cytotoxic) antibodies were regularly found in rejecting canine renal allografts. Techniques for the elution and characterization of these antibodies and other immunologically reactive substances from kidneys undergoing rejection are described. Physicochemical characteristics of the antibodies eluted from rejecting homografts conform to the electrophoretic and ultracentrifugal criteria for 19 S (IgM) and 7 S (IgG) immunoglobulins. Biologic activity of these antibodies includes a preferential affinity for donor kidney antigen as well as cross-reactivity with antigen from “indifferent donors.” Consistent demonstration of affinity for host antigen helps substantiate the concept of autoimmunity in allograft rejection. Antibody cross-reacted best with donor lung and platelets and had lesser reactivity against donor bladder, liver and spleen. A small molecular weight complement fixing substance was found in all rejecting kidneys, but it was not present in normal tissue. This dialyzable substance inactivates complement when reacted with kidney or platelet “antigen” but exhibits no donor specific affinity. A large molecular weight inhibitor of complement hemolytic activity was regularly found in all kidney tissue, rejected or normal.