The HLA complex and coeliac disease

Area of Science:

• Immunogenetics
• Gastroenterology
• Autoimmune Diseases

Background:

• Human Leukocyte Antigen (HLA) genes play a critical role in the development and pathogenesis of coeliac disease (CD).
• HLA-DQA1 and HLA-DQB1 genes encode the HLA-DQ heterodimer, the primary genetic predisposing factor for CD.
• Approximately 90% of CD patients carry the HLA-DQ2.5 heterodimer, with others having lower-risk variants like HLA-DQ8, HLA-DQ2.2, or HLA-DQ7.5.

Purpose of the Study:

• To elucidate the role of HLA genetics in coeliac disease pathogenesis.
• To highlight the diagnostic utility of HLA typing in coeliac disease.
• To explore the association between HLA genotypes and CD-related features and gut microbiota.

Main Methods:

• Analysis of Human Leukocyte Antigen (HLA) gene associations with coeliac disease.
• Characterization of HLA-DQ heterodimers and their peptide-binding affinities.
• Review of studies linking HLA genotypes to clinical outcomes, antibody levels, and histological findings.

Main Results:

• Specific HLA-DQ molecules, particularly HLA-DQ2.5, exhibit high affinity for deamidated gluten peptides, initiating the immune response in CD.
• HLA typing demonstrates a high negative predictive value for coeliac disease diagnosis.
• Associations between HLA risk and CD features like age at onset, clinical outcomes, antibody levels, and histological grade are suggested, requiring further investigation.

Conclusions:

• HLA genetics is fundamental to coeliac disease pathogenesis and diagnosis.
• HLA typing offers significant diagnostic support due to its high negative predictive value.
• Further research is warranted to fully understand the influence of HLA-DQ genotypes on CD characteristics and gut microbiota composition.