Allergic reactions to a horse globulin therapy and their prevention by induction of immunological tolerance

In a number of 127 patients the compatibility of a therapy with horse antihuman lymphocytic globulin (HAHLG) has been studied. The patients received HAHLG for several reasons: 74 patients with organ transplants; 18 patients with chronic lymphatic leukemia, 35 patients with autoimmune diseases were treated. Before the beginning of the intravenous HAHLG therapy induction of immunological tolerance respectively unresponsiveness against horse globulin was tried by giving 10 mg/kg body weight ultracentrifuged normal horse IgG 6 days and 30 mg/kg body weight 3 days before the first ALG application. During ALG therapy continuous immunological controls were performed: immunodiffusion, hemagglutination, passive hemagglutination and skin tests. The appearance of possible allergic reactions was registered carefully. After ALG treatment the immune response to horse IgG was studied by the antigen elimination technique. The hematological and immunological findings could be correlated to the clinical symptoms. Together with allergic reactions as urticaria or serum nephritis or arthritis there was always an increase in the hemagglutinating and passive hemagglutinating titers observed; furthermore, precipitating antibodies could be detected. The change from a negative to a positive skin test with normal horse IgG proved to be a reliable method in detecting a beginning allergic reaction. While 12 out of 14 patients with a positive skin reaction showed clinical signs of allergy, patients with negative skin tests were almost free of such symptoms. Apart from the purification of the globulin the mode of application influenced the frequency of allergic reactions significantly. By the induction of immunological tolerance against horse IgG as well as the ultracentrifugation of the globulin prior to administration serious allergic reaction could be avoided. This is demonstrated by the comparison of 2 groups of patients, who were treated with (II) or without (I) induction of immunological tolerance. Serious complications as anaphylactic shock (2), serum nephritis (3), serum arthritis (4), urticaria (9) were only seen in group I, whereas the patients of group II were almost free of allergic symptoms. Summarizing the immunological findings and the frequency of clinical allergies the trial to induce immunological unresponsiveness against horse IgG was successful in 80% of the patients. By observations of the proposed application schedule the risk of a horse globulin therapy can be minimized.