Autoimmune hemolytic anemia (AHA) is not a rare occurence, especialy among patients with lymphoreticular malignancies, leukemias, and certain mestastic carcinomas. Correlation of the severity of the hemolytic process with quantitation of immunoglobulin and/or complement subcomponents bound to the red blood cell (RBC) membrane enhances understanding of the pathopysiology of this disorder and provides criteria for judging the success or failure of therapy. Allo-immune hemolysis in multitransfused patients, may complicate their management, requiring well characterized serologic reagents and reliable quantitative methods for resolution of associated transfusion problems. Relevant to the above, this investigative program will: a) continue its emphasis on improving the quality and performance of specific anti-immunoglobulin and anti-complement reagents, b) expand application of the labelled purified reagents to quantitation of cell bound IgG and complement (principally C3d) on RBC cated by auto-and/or allo-immune mechanisms, c) persist in efforts to verify the molar combining ration of antiglobulin antibodies with RBC-bound immunoglobulin and complement so that the bound immunoproteins may be expressed in absolute terms (molecules/cell), d) develop and characterize the performance of monoclonal anti-IgG and anti-C3d antibodies to be used for the above purposes and compare the results with those provided by polyclonal antibodies, e) explore the applicability of quantitative anti-monoclonal and anti-polyclonal anti-antiglobulin methods to auto- and alloimmune hemolytic problems, f) compare the use of enzyme-conjugated and fluorescein-conjugated antibodies with conventional radiolabeled antibodies for achieving the diagnostic and quantitative aims alread mentioned. Analogous auto- and allo-immune in vivo platelet destruction is not uncommon especially in multitransfused patients undergoing aggressive chemotherapeutic treatment for malignant disease. Accordingly, the polyclonal and monoclonal reagents and quantitative methods developed in relation to immune-mediated RBC destruction will be adapted in relation to immune platelet destruction. Special emphasis will be given to developing an RIA screening assay for early detection of alloantibodies to HLA-related and platelet-specific antigens. Most important, an RIA compatibility test will be developed for pretransfusion platelet cross-matching, its effectiveness to be verified by in vivo survival studies of 111 in-labelled donor platelets.
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