When type 1 diabetes meets celiac disease

Area of Science:

• Immunogenetics
• Autoimmune Diseases

Background:

• Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune disorders that can co-occur.
• Human Leukocyte Antigen (HLA) alleles, specifically HLA-DQ2 and HLA-DQ8, are established genetic risk factors for both T1D and CD.

Purpose of the Study:

• To investigate the HLA genetic profiles of patients with co-existing T1D and CD.
• To identify specific HLA genotypes associated with the simultaneous development of T1D and CD.

Main Methods:

• Analysis of HLA allele frequencies and ancestral haplotypes in Slovenian patients with T1D, CD, and co-existing T1D+CD.
• Comparison of HLA profiles between patient groups to determine shared and distinct genetic predispositions.

Main Results:

• Patients with co-existing T1D and CD (T1D+CD) exhibited HLA profiles more similar to T1D patients than CD patients.
• The HLA-DQ2 allele conferred a higher risk for developing both T1D and CD compared to HLA-DQ8.
• The ancestral haplotype A1-B8-DR3-DQ2-MICA*008 (8.1AH) was over-represented in Slovenian T1D+CD patients, with B*08 being a significant independent risk factor.
• Specific genotypes, DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8, were associated with increased risk for CD in T1D patients and T1D in CD patients, respectively.

Conclusions:

• HLA-DQ2 is a significant risk factor for the co-occurrence of T1D and CD.
• Certain HLA genotypes, particularly DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8, identify individuals at higher risk for developing both autoimmune diseases.
• Consideration of targeted screening for the second disease in patients with the first, especially those with low-risk genotypes, may be beneficial.