The immune response in individuals with hla-dr specificities conferring susceptibility to insulin-dependent diabetes - A hypothesis
Summary, in English
The genetic control of insulin-dependent diabetes as well as of other autoimmune endocrine disorders have not been defined. These disorders are often said to run in families but the mode of inheritance is not understood. A most intriguing aspect of insulin-dependent diabetes is its close association with the HLA-DR specificities 3 and/or 4. More than 90% of all caucasian IDDM have either one or both of these haplotypes. Even more intriguing is the observation that about 50% of the insulin-dependent diabetic patients are HLA-DR3/4 positive. This haplotype is present in the background population at a frequency of only 2-4% while the DR3 and/or 4 specificities are found among nearly 60%. While the DR3 and/or 4 specificities are necessary for insulin-dependent diabetes to develop, their high frequency in the background population does not permit HLA-DR typing to be useful as a marker neither for autoimmune reactions nor to predict diabetes. This is particularly evident from the fact that less than 50% of monozygotic twins are concordant for IDDM. However, there is evidence to suggest that immune responsiveness to certain antigens is associated with different HLA specificities. It is therefore speculated that in the course of an immune response to an invading antigen (virus, bacterium, etc.), the combination of the specific MHC class II molecule and this invading antigen on an antigen presenting cell, results in the formation of effector cells such as plasma cells and cytotoxic T lymphocytes that also cross-react with the pancreatic B cells. Depending on the strength of this reaction, which may involve multiple exposures to the same or related antigens, pancreatic B cells are damaged to varying degree eventually leading to the development of IDDM.
Journal article review
- Endocrinology and Diabetes
- ISSN: 0265-5985