LACK OF IMMUNE RESPONSIVENESS TO BOVINE SERUM-ALBUMIN IN INSULIN-DEPENDENT DIABETES

Background. Epidemiologic studies have implicated the ingestion of cow 's milk in the pathogenesis of insulin-dependent diabetes mellitus (ID DM). Moreover, in a recent study, 100 percent of patients with new-ons et IDDM had antibodies against bovine serum albumin (BSA), with a majo rity directed against a 17-amino-acid BSA peptide (ABBOS). Cellular im mune mechanisms are thought to be the principal mediators of pancreati c beta-cell destruction in IDDM. Methods. We measured the responses of peripheral-blood mononuclear cells to BSA and ABBOS or serum IgG anti -BSA antibodies (by particle-concentration fluorescence immunoassay) i n 71 patients with IDDM, 55 subjects at various degrees of risk for ID DM, 36 patients with other autoimmune disorders (chronic autoimmune th yroiditis, rheumatoid arthritis, and systemic lupus erythematosus), an d 48 normal subjects. Results. The responses of peripheral-blood monon uclear cells to BSA or ABBOS were positive in 2 of 24 patients with ne w-onset IDDM, 1 of 25 first-degree relatives of patients with IDDM who were negative for islet-cell antibodies, 2 of 30 first-degree relativ es of patients with IDDM who were positive for islet-cell antibodies, 1 of 28 patients with established IDDM, and 1 of 29 normal subjects. S imilarly, anti-BSA antibodies were not detected significantly more oft en in patients with new-onset IDDM (3 of 31, 10 percent) than in norma l subjects (1 of 37, 3 percent; P = 0.32). However, many patients with autoimmune disease and subjects at increased risk for IDDM had anti-B SA antibodies (frequency, 10 to 31 percent). Conclusions. Anti-BSA ant ibodies may reflect a general defect in the process of immunologic tol erance associated with a predisposition to autoimmunity rather than im munity specific to beta cells. The absence of cellular immunity to BSA and ABBOS in IDDM does not support a role for this antigen in the pat hogenesis of the disorder.