Genetic and non-genetic risk factors associated with pediatric celiac disease [TEDDY study]
1. Children with the HLA haplotype DR3-DQ2 were at a higher risk for developing celiac disease autoimmunity and celiac disease by 5 years of age.
2. Female gender, Swedish residence, and having a first-degree relative with celiac disease were associated with a higher risk of developing celiac disease autoimmunity.
Evidence Rating Level: 2 (Good)
Study Rundown: Celiac disease is an autoimmune condition where mucosal damage and villous atrophy occur in response to the consumption of gluten. The Environmental Determinants of Diabetes in the Young (TEDDY) study investigated the genetic risk of type 1 diabetes as well as celiac disease in children in the United States, Finland, Germany, and Sweden. This study involved a large, multinational cohort and followed children at high risk of developing type 1 diabetes or celiac disease over the course of their early childhood.
The results described here found that the HLA haplotype DR3-DQ2 was associated with a higher risk of developing celiac disease autoimmunity and celiac disease. Children who were homozygous for DR3-DQ2 had greater than 5 times the risk of developing autoimmunity or celiac disease compared to DR4-DQ8 homozygotes. Non-genetic risk factors were also identified and include having a first-degree relative with celiac disease and residence in Sweden. These genetic and non-genetic risk factors may be useful in guiding the screening of infants at high risk for celiac disease. Further study of environmental risk factors may contribute to a better understanding of the development of this condition.
Click to read the study, published today in NEJM
Click to read an accompanying perspective in NEJM
In-Depth [prospective cohort]: After screening 424,788 newborns, the TEDDY study included 6403 children who carried one of 4 HLA genotypes of interest. These children had tTG antibody testing at least once over a median follow-up of 60 months. The primary outcome was the development of celiac disease autoimmunity defined as two consecutive positive tests for tTG antibody. The secondary outcome was celiac disease diagnosed by biopsy or by two consecutive tTG antibody tests with a mean antibody level of 100 units or higher.
The primary outcome occurred in 786 (12%) of the children included and a diagnosis of celiac disease was made in 312 children. The cumulative risk of developing celiac disease autoimmunity by age 5 years was highest among children who were homozygous for the DR3-DQ2 haplotype at 26%, followed by 11% in those with the DR3-DQ2/DR4-DQ8 haplotype, 9% in those who were homozygous for the DR4-DQ8 haplotype, and 2% in those with the DR4-DQ8/DR8-DQ4 haplotype (P<0.001 for all comparisons). The study identified three non-genetic factors associated with a significantly higher risk of developing celiac disease autoimmunity: having a first-degree relative with celiac disease, female gender, and Swedish residence (P<0.001 for all comparisons).
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