Cell-mediated immune response to β casein in recent-onset insulin-dependent diabetes: implications for disease pathogenesis

Background The cowsʹ milk hypothesis for the cause of insulin-dependent diabetes (IDDM) is based on the concept that early consumption of cowsʹ milk may expose the immune system to a foreign protein possessing immunological cross-reactivity with an antigen present on pancreatic (3-cells. Methods We measured in-vitro peripheral lymphocyte response to β casein, a protein in cowsʹ milk, in 47 patients with recent-onset IDDM, in 36 healthy people and, to test disease specificity, in 10 patients with autoimmune thyroid disease. Other antigens tested for were bovine serum albumin, purified protein derivative, human serum albumin, and phytohaemagglutinin. Results Specific proliferation of T lymphocytes with bovine β casein was seen in patients with IDDM (mean [SD] age 18·7 [9]) with a significant difference in mean stimulation index (SI) versus healthy people (p<0·00001) or patients with autoimmune thyroid disease (p<0·002). 24 of 47 (51 1%) patients with IDDM versus 0/10 patients with thyroid disease and 1/36 (2·7%) healthy people had a positive response to β casein defined as a SI above the mean value +2 SD of healthy people (p<0·00001). No significant differences were observed between the groups of subjects with respect to other antigens tested. Interpretation The association between IDDM and early consumption of cowsʹ milk may be explained by the generation of a specific immune response to β casein. Exposure to cowsʹ milk triggers a cellular and humoral anti-β casein immune response which may cross-react with a beta-cell antigen. It is of interest that sequence homologies exist between β casein and several β-cell molecules.