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Insulin autoimmunity: the rate limiting factor in pre-type I diabetes
G S Eisenbarth1, R A Jackson, A Pugliese
1Section of Immunology & Immunogenetics, Joslin Diabetes Center, Harvard Medical School, Massachusetts.
Journal of Autoimmunity
|April 1, 1992
Summary
Autoantibodies to insulin are early indicators of type I diabetes progression. High levels, especially with DR4 expression, suggest a central role in islet autoimmunity development.
Area of Science:
- Immunology
- Endocrinology
- Diabetology
Background:
- Type I diabetes (TID) is an autoimmune disease characterized by islet cell destruction.
- Autoantibodies, including islet cell antibodies (ICA), precede TID onset.
- New subtypes of ICA, 'restricted' and 'non-restricted', have been identified.
Purpose of the Study:
- To investigate the role of insulin autoantibodies (IAA) in the early stages of type I diabetes.
- To determine the relationship between IAA levels, other autoantibodies, and disease progression.
- To explore the association between IAA, HLA-DR4 expression, and the development of anti-islet autoimmunity.
Main Methods:
- Detection and quantification of autoantibodies in prediabetic individuals.
- Correlation analysis of autoantibody levels with the rate of progression to type I diabetes.
- Analysis of autoantibody levels in relation to HLA-DR4 expression.
Main Results:
- Antibodies to insulin are unique among autoantibodies in prediabetics due to their correlation with the rate of progression to type I diabetes.
- IAA levels appear to be stably regulated before the appearance of ICA.
- Highest IAA levels are associated with HLA-DR4 expression.
Conclusions:
- An immune response to insulin is hypothesized to be an early and central feature of anti-islet autoimmunity.
- When combined with loss of tolerance to other islet antigens (like ICA), this immune response to insulin is considered pathogenic.
- IAA may serve as a critical early marker for type I diabetes development.