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

Background and objective: The hypothesis that cow's milk components may con stitute environmental factors in the pathogenesis of insulin-dependent diab etes mellitus (IDDM) is increasingly gaining in importance. This study for the first time determined, in a family study, antibodies against the most c ommon 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 c orrelation between A1 and A2 antibodies and age (p < 0.001). Increased amou nts of anti-casein A1 antibodies were found among patients with IDDM and th eir siblings. On the other hand, the serum samples from parents and control persons contained antibodies against the A2 variant. The preferential bind ing of sera to the one or other casein variant was in all four groups stati stically 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 hypot hesis of a defective oral immunotolerance to cow's milk antigens in IDDM.