Immune complexes (IC) are formed in the circulation or in tissue fluids as a consequence of the interaction between antigens and their corresponding antibodies (Ab). Many properties of IC, including clearance from the circulation, complement fixation, and adherence to phagocytes, depend on IC size and composition. The chronic presence of IC has been implicated in the pathology of several diseases including systemic lupus erythematosus, rheumatoid arthritis, and neoplastic disease. The demonstration that activity which blocks the immune response to tumors can be removed by incubation of serum with protein A has motivated studies of plasma adsorption onto immobilized protein A in a number of tumor systems. Excellent success has been reported in treatment of lymphosarcoma and leukemia in FeLV-infected cats, and variable success has been reported in clinical studies with humans having a variety of neoplastic disease. No systematic study to delineate the myriad reactions occurring during immunoadsorption treatment of plasma has been undertaken. A more complete understanding of the phenomena must be attained if this technique is to be advanced in application to IC and Ab-mediated diseases. Our research objectives are to: (1) determine the parameters that govern size, composition, and structure of IC, (2) investigate and dependence of IC size and composition on binding and activation of complement, and (3) define the reactions that occur upon contact of IC with immunoadsorbents such as immobilized protein A. Model IC constructed from two or more monoclonal Ab and bovine serum albumin will be characterized in terms of a variety of physicochemical properties, including molecular weight and size distribution, composition, overall structure, and mean hydrodynamic radius using electron microscopy, quasi-elastic and classical light scattering, small angle neutron scattering, high performance liquid chromatography, radioimmunoassays, and mathematical models. Purified complement components will be incubated with model IC; the dependence of complement fixation and activation on IC size, structure, and com- position will be measured. Similarly, IC will be incubated with immunoadsorbents to analyze adsorption effects. These fundamentals studies will provide the basis for experiments using IC isolated from sera of FeLV-infected cats. The proposed research will enhance our understanding of IC formation and behavior and will provide a rational basis for development and design of immunoadsorption techniques which may be applied diagnostically or therapeutically to a variety of disease states.
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