Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Celiac disease autoimmunity development involves genetic and environmental factors.
• The season of birth is a potential environmental influence on celiac disease risk.
• Early-life immune responses are critical in the pathogenesis of autoimmune diseases.

Purpose of the Study:

• To investigate biological pathways linking season of birth to celiac disease autoimmunity.
• To explore interactions between season of birth, genetics, and early-life factors in celiac autoimmunity.
• To gain insights into the early pathogenesis of celiac disease.

Main Methods:

• Long-term follow-up of 6523 genetically predisposed children in the TEDDY birth cohort study.
• Prospective sampling and data collection across six international research centers.
• Definition of celiac disease autoimmunity based on consecutive positive tissue transglutaminase antibody tests.

Main Results:

• A significant effect of season of birth on celiac autoimmunity risk was observed.
• This effect was dependent on polymorphisms in the CD247 gene (SNP rs864537A>G).
• Interactions between CD247 variants, season of birth, and early-life febrile infections were identified.

Conclusions:

• CD247 gene variants modify the impact of season of birth on celiac autoimmunity risk.
• Interactions between CD247, season of birth, and infections highlight complex gene-environment interplay.
• Findings suggest CD247 variants are relevant for future celiac disease gene-environment studies.