Human renal allografts: Glomerular deposits of horse immunoglobulin G and nephritis following administration of antilymphocyte globulin

Abstract

The administration of horse antilymphocyte globulin (ALG) containing glomerular basement membrane (GBM) cross-reactive antibody has the potential for inducing nephritis of the anti-GBM (linear) type. Similarly, a hostantihorse antibody response to the ALG may result in antigen-antibody complex (granular) nephritis. GBM cross-reactive antibody is more likely to be present in ALG derived from horses immunized with suspensions of lymph modes or thymus than with washed lymphoid cell suspensions, possibly because of the presence of other tissue antigens. However, ALG derived from some of our horses immunized with washed human thoracic duct lymphocytes also contained antibody cross-reactive with human GBM. Such antibody was found to be intermittently present in subsequent bleeds (ALG lots) following its demonstration in initial or early ALG lots. An ALG lot submitted for our evaluation of its possible GBM cross-reactivity was strongly positive but showed a marked reduction in cross-reactivity during extended storage at −20°C. Therefore, each lot of ALG should be tested for the presence of GBM cross-reactive antibody immediately after preparation. Of 58 renal allograft recipients treated intramuscularly with ALG and other immunosuppressants, allograft biopsies were taken for specific indications in 32. Examination of these biopsies for deposits of horse immunoglobulin G (IgG) showed that two contained linear deposits, suggesting that the cross-reactive antibody had not been completely absorbed locally following intramuscular administration. One of the latter two immunosuppressed recipients developed nephritis, probably a result of GBM cross-reactive antibody, from which he subsequently recovered. Although not all patients who received ALG containing GBM cross-reactive antibody develop clinically significant nephritis, until more data are available regarding the nephrotoxic effects of ALG, only lots found not to contain such antibody should be used clinically.