Preventing Antibody Formation to Anti-Lymphocytic Globulin in Man

One or more doses of equine IgG either as anti-lymphocytic globulin (ALG) or deaggregated normal equine IgG (DEGG) were given to 73 individuals including 43 potential or actual allograft recipients, 10 patients with leukemia and 20 normal volunteers in order to define conditions which would prevent formation of detectable antibodies to horse IgG in patients being treated with ALG. Formation of antibody was measured by studying the plasma clearance of radioactively-labeled horse IgG and by an immunoadsorbent assay. DEGG and ALG were equally immunogenic when either was given alone, causing antibody formation to horse IgG in 20 of the 27 patients (74%) treated with one or the other agent. Moreover, treatment of patients with ALG given along with maximum tolerated doses of azathioprine and methyl prednisolone did not reduce the incidence of antibody formation to horse IgG. In contrast, 8 of 27 patients (30%) who were given chemical immunosuppressive treatment for at least 2 days followed by 2 to 18 daily intravenous injections containing 50 µg/Kg of DEGG developed detectable antibodies to horse IgG when subsequently treated with ALG. Of these 8, only 1 developed rapid immune elimination of labeled horse IgG. These results suggest that it is now possible to evaluate the toxic effects and therapeutic efficacy of ALG in man free of those manifestations which might otherwise be ascribed to allergic reactions.