Celiac Disease Risk -TEDDY Study

“The Environmental Determinants of Diabetes in the Young (TEDDY) is a multinational study that follows children at high genetic risk for type 1 diabetes, with the development of celiac disease as a secondary outcome.”  A recent publication provides excellent data with regard to the longitudinal risk of developing celiac disease (CD) (NEJM 2014; 371: 42-9).

Methods: 424,788 newborns were screened for at-risk HLA genotypes (from 2004 to 2010) in four countries (U.S, Finland, Germany, and Sweden).  21,589 had one of nine HLA genotypes of interest to the investigators –>8677 infants were enrolled in the study; 6403 of this group had one of the four HLA genotypes reported in this study:

  1. DR3-DQ2 homozygotes
  2. DR3-DQ2/DR4-DQ8
  3. DR4-DQ8 homozygotes
  4. DR4-DQ8/DR8-DQ4

Median follow-up: 60 months

Definitions for study:

  • Celiac autoimmunity: presence of tTG antibodies on two consecutive tests at least 3 months apart
  • Celiac disease: CD diagnosis based on biopsy (Marsh 2 or higher) or persistently high tTG (≥100 units) on at least two tests at least 3 months apart

Key findings:

  • Overall 786 children developed celiac autoimmunity (12%) and 291 had confirmed CD.
  • Children with DR3-DQ2 homozygosity had more than 5 times the risk of CD than the lowest-risk groups; in addition, the risk was 2.5 times more than the risk for a heterozygote (single DR3-DQ2) haplotype.
  • By 5 years of age, celiac autoimmunity developed in 26% and 12% respectively among children with DR3-DQ2 homozygosity  and in 11% and 3% of those children with DR3-DQ2 heterozygosity.
  • Residence in Sweden increased risk for CD with hazard ratio of 1.9.  The fact that residents with same genetic haplotypes had increased risk suggests that an environmental factor is playing a role.  It was noted that these children were given gluten-containing cereals at the earliest age.
  • CD was more common in females with HR of 2.16 (P<0.001) and in those with family history of CD HR 2.95 (P<0.001)

Take-home message: This prospective TEDDY study is providing useful information about how likely an individual with a genetic predisposition will develop CD and how quickly this develops.

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