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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
Extreme genetic risk for type 1A diabetes
Theresa A Aly1, Akane Ide, Mohamed M Jahromi
1Barbara Davis Center for Childhood Diabetes and Human Medical Genetics Program, University Colorado Health Sciences Center, Aurora, CO 80045, USA.
Summary
Type 1A diabetes (T1D) risk is significantly higher in siblings who share both HLA haplotypes with their affected family member, especially those with the DR3/4-DQ8 genotype. This finding allows for early identification of high-risk individuals for preventative trials.
Area of Science:
- Immunogenetics
- Endocrinology
- Pediatric Autoimmunity
Background:
- Type 1A diabetes (T1D) is an autoimmune disease influenced by specific Human Leukocyte Antigen (HLA) DR/DQ alleles.
- The DR3/4-DQ8 heterozygous genotype is associated with the highest T1D risk.
- Understanding genetic inheritance patterns is crucial for predicting T1D development.
Purpose of the Study:
- To determine the role of HLA-DR and -DQ genotypes in T1D risk among siblings.
- To analyze HLA haplotype sharing between T1D patients and their siblings.
- To identify high-risk individuals for early intervention strategies.
Main Methods:
- Genotyping of HLA-DR and -DQ alleles at birth in siblings of T1D patients.
- Analysis of identical-by-descent HLA haplotype sharing.
- Clinical follow-up for anti-islet autoimmunity and T1D progression.
Main Results:
- Siblings sharing both HLA haplotypes with a T1D proband showed dramatically increased risk for islet autoimmunity (85% by age 15).
- 55% of DR3/4-DQ8 siblings sharing both HLA haplotypes developed T1D by age 12, versus 5% sharing fewer.
- Even without the DR3/4-DQ8 genotype, sharing both HLA haplotypes increased T1D risk by age 12.
Conclusions:
- T1D inheritance is strongly linked to HLA-DR/DQ alleles and other MHC-linked genes.
- Identical-by-descent HLA haplotype sharing is a major determinant of T1D risk.
- Early identification of high-risk siblings is possible for preventative therapeutic trials.
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