Significance of A1 and A2 antibodies against β-casein in insulin-dependent diabetes mellitus

Background and objective: The hypothesis that cow's milk components may constitute environmental factors in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is increasingly gaining in importance. This study for the first time determined, in a family study, antibodies against the most common variants of the beta-casein (A1 and A2), Patients and methods: A total of 1 257 sera - from 287 patients with IDDM, 386 siblings, 477 individual parents and 107 healthy controls - were tested by enzyme-linked immunosorbent assay (ELISA) for anti-beta casein A1- and A2-IgG antibodies. Results: Antibodies against casein were present in all four groups, highest titres being found in diabetics. In all four groups there was an inverse correlation between A1 and A2 antibodies and age (p < 0.001). Increased amounts of anti-casein A1 antibodies were found among patients with IDDM and their siblings. On the other hand, the serum samples from parents and control persons contained antibodies against the A2 variant. The preferential binding of sera to the one or other casein variant was in all four groups statistically significant (p < 0.001). Conclusion: Because the A1 variant of beta-casein correlates with the onset of IDDM, but can also occur in normal controls, this may confirm the hypothesis of a defective oral immunotolerance to cow's milk antigens in IDDM.