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Published on: June 16, 2011
Cell-mediated immune response to beta casein in recent-onset insulin-dependent diabetes: implications for disease
M G Cavallo1, D Fava, L Monetini
1Cattedra di Endocrinologia (I), Policlinico Umberto I, University of Rome, La Sapienza.
Insights
Early cow's milk consumption may trigger an immune response linked to insulin-dependent diabetes (IDDM). Researchers found specific T-lymphocyte reactions to beta-casein in IDDM patients, suggesting a cross-reaction with pancreatic beta-cells.
Area of Science:
- Immunology
- Endocrinology
- Diabetes Research
Background:
- The cows' milk hypothesis suggests early cow's milk intake may trigger autoimmune responses leading to insulin-dependent diabetes (IDDM).
- This hypothesis is based on potential immunological cross-reactivity between cow's milk proteins and pancreatic beta-cell antigens.
Purpose of the Study:
- To investigate the association between cow's milk protein exposure and the immune response in patients with recent-onset IDDM.
- To determine if the immune response to cow's milk protein is specific to IDDM.
Main Methods:
- Measured in-vitro peripheral lymphocyte response to beta-casein in 47 IDDM patients, 36 healthy controls, and 10 patients with autoimmune thyroid disease.
- Tested responses to other antigens including bovine serum albumin, purified protein derivative, human serum albumin, and phytohaemagglutinin for specificity.
Main Results:
- Significantly higher T-lymphocyte proliferation to beta-casein was observed in IDDM patients compared to healthy individuals (p < 0.00001) and thyroid disease patients (p < 0.002).
- 51.1% of IDDM patients showed a positive response to beta-casein, versus 2.7% of healthy individuals and 0% of thyroid disease patients (p < 0.00001).
- No significant differences in lymphocyte response were found for other tested antigens between groups.
Conclusions:
- The findings support the cows' milk hypothesis by demonstrating a specific immune response to beta-casein in IDDM patients.
- This cellular and humoral anti-beta-casein immune response may cross-react with pancreatic beta-cell antigens, potentially contributing to IDDM development.
- Observed sequence homologies between beta-casein and beta-cell molecules warrant further investigation into the mechanism of cross-reactivity.
Background:
The cows' milk hypothesis for the cause of insulin-dependent diabetes (IDDM) is based on the concept that early consumption of cows' milk may expose the immune system to a foreign protein possessing immunological cross-reactivity with an antigen present on pancreatic beta-cells.
Methods:
We measured in-vitro peripheral lymphocyte response to beta casein, a protein in cows' 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 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 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 beta 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 cows' milk may be explained by the generation of a specific immune response to beta casein. Exposure to cows' milk triggers a cellular and humoral anti-beta casein immune response which may cross-react with a beta-cell antigen. It is of interest that sequence homologies exist between beta casein and several beta-cell molecules.
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