CELL-MEDIATED IMMUNE-RESPONSE TO BETA-CASEIN IN RECENT-ONSET INSULIN-DEPENDENT DIABETES - IMPLICATIONS FOR DISEASE PATHOGENESIS

Background The cows' milk hypothesis for the cause of insulin-dependen t diabetes (IDDM) is based on the concept that early consumption of co ws' milk may expose the immune system to a foreign protein possessing immunological cross-reactivity with an antigen present on pancreatic b eta-cells. Methods We measured in-vitro peripheral lymphocyte response to beta casein, a protein in cows' milk, in 47 patients with recent-o nset IDDM, in 36 healthy people and, to lest disease specificity, in 1 0 patients with autoimmune thyroid disease. Other antigens tested for were bovine serum albumin, purified protein derivative, human serum al bumin, and phytohaemagglutinin. Results Specific proliferation of T ly mphocytes with bovine beta 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 autoimmu ne thyroid disease (p<0.002). 24 of 47 (51.1%) patients with IDDM vers us 0/10 patients with thyroid disease and 1/36 (2.7%) healthy people h ad a positive response to beta casein defined as a SI above the mean v alue +2 SD of healthy people (p<0.00001). No significant differences w ere observed between the groups of subjects with respect to other anti gens tested. Interpretation The association between IDDM and early con sumption of cows' milk may be explained by the generation of a specifi c immune response to beta casein. Exposure to cows' milk triggers a ce llular and humoral anti-beta casein immune response which may cross-re act with beta-cell antigen. it is of interest that sequence homologies exist between beta casein and several beta-cell molecules.