Seven years' experience with antilymphoblast globulin for renal transplantation from cadaver donors. 1976

J S Najarian, and R L Simmons, and R M Condie, and E J Thompson, and D S Fryd, and R J Howard, and A J Matas, and D E Sutherland, and R M Ferguson, and J R Schmidtke

Antibody of the IgGab type can be isolated from horses immunized with cultured human lymphoblasts plus complete Freund's adjuvant. The essential steps for the production of a safe, potent anti-human lymphoblast globulin (ALG) are: A) the use of early bleedings after immunization to reduce the titer of antibodies which react with red blood cells and platelets; B) careful absorption with human red blood cell stroma and platelets; C) stabilization with non-crystalline silica dioxide; D) chromatography through QAE sephadex to remove pyrogens, microaggregates and possible inhibitors of ALG activity; E) careful safety testing in animals for toxicity and pyrogenicity; and F) testing in vitro for sterility. Such a purified horse ALG (IgGab) can be administered safely intravenously to patients to supplement a standardized immunosuppressive regimen incorporating azathioprine and prednisone. Under these circumstances, allergic reactions are very rare, antibodies to horse IgG do not develop, skin tests to horse IgG remain negative, and immune elimination of circulating horse IgG from the human circulation cannot be demonstrated. The overall results of ALG patient survival and transplant function after 184 consecutive first cadaver transplants at the University of Minnesota demonstrate a statistically significant improvement in both parameters accompanying increases in ALG dose while rigidly utilizing standardized doses of azathioprine and prednisone. There is a significant reduction in the number of grafts lost to rejection; significant reduction in the number of rejection episodes; significant delay in the onset of rejection episodes; but there is no increase in septic loss of patients or kidneys. These efforts could be seen in the gross data or when subgroups controlling for patient age, tissue typing were analyzed. Excluding patients at high risk did not alter the results. The beneficial effects of ALG were particularly striking in good matches. In the highest doses, ALG may be dangerous for older patients with poor matches who develop an increased incidence of septic loss of kidney and/or life. Thus, ALG appears to be a useful adjunct in the early management of cadaver transplants by reducing the incidence and frequency of rejection episodes. The dose should probably be reduced in the older patients who receive kidneys from badly mismatched donors. One cannot conclude from this study that ALG manufactured in other centers by this or other techniques, will accomplish the same results since the multiplicity of factors involved in the success and failure of transplants must be controlled so that the influence of intravening variables in the assessment of ALG effectiveness can be assessed.

UI MeSH Term Description Entries
D006967 Hypersensitivity Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D002102 Cadaver A dead body, usually a human body. Corpse,Cadavers,Corpses
D006650 Histocompatibility Testing Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed) Crossmatching, Tissue,HLA Typing,Tissue Typing,Crossmatchings, Tissue,HLA Typings,Histocompatibility Testings,Testing, Histocompatibility,Testings, Histocompatibility,Tissue Crossmatching,Tissue Crossmatchings,Tissue Typings,Typing, HLA,Typing, Tissue,Typings, HLA,Typings, Tissue
D006680 HLA Antigens Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases. Human Leukocyte Antigen,Human Leukocyte Antigens,Leukocyte Antigens,HL-A Antigens,Antigen, Human Leukocyte,Antigens, HL-A,Antigens, HLA,Antigens, Human Leukocyte,Antigens, Leukocyte,HL A Antigens,Leukocyte Antigen, Human,Leukocyte Antigens, Human
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000961 Antilymphocyte Serum Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION. ATGAM,Antilymphoblast Globulins,Antilymphocyte Antibodies,Antilymphocyte Globulin,Lymphocytotoxic Antibodies,Anti-Thymocyte Globulin,Antilymphocyte Immunoglobulin,Antithymocyte Globulin,Antithymoglobulin,Lymphocyte Immune Globulin, Anti-Thymocyte Globulin,Lymphocyte Immune Globulin, Anti-Thymocyte Globulin (Equine),Pressimmune,Anti Thymocyte Globulin,Anti-Thymocyte Globulins,Antibodies, Antilymphocyte,Antibodies, Lymphocytotoxic,Antibody, Antilymphocyte,Antibody, Lymphocytotoxic,Antilymphoblast Globulin,Antilymphocyte Antibody,Antilymphocyte Globulins,Antilymphocyte Immunoglobulins,Antilymphocyte Serums,Antithymocyte Globulins,Antithymoglobulins,Globulin, Anti-Thymocyte,Globulin, Antilymphoblast,Globulin, Antilymphocyte,Globulin, Antithymocyte,Globulins, Anti-Thymocyte,Globulins, Antilymphoblast,Globulins, Antilymphocyte,Globulins, Antithymocyte,Immunoglobulin, Antilymphocyte,Immunoglobulins, Antilymphocyte,Lymphocyte Immune Globulin, Anti Thymocyte Globulin,Lymphocytotoxic Antibody,Serum, Antilymphocyte,Serums, Antilymphocyte
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic
D016030 Kidney Transplantation The transference of a kidney from one human or animal to another. Grafting, Kidney,Renal Transplantation,Transplantation, Kidney,Transplantation, Renal,Kidney Grafting,Kidney Transplantations,Renal Transplantations,Transplantations, Kidney,Transplantations, Renal

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