High incidence of Celiac Dis. in a Long-term Study of Ado. With Suscep Genotypes

[dr.j.cardey@wanadoo.fr]

High incidence of Celiac Disease in a Long-term Study of Adolescents With Susceptibility Genotypes

Edwin Liu
Fran Dong
Anna E. Barón
Iman Taki
Jill M. Norris
Brigitte I. Frohnert
Edward J. Hoffenberg
Marian Rewers

Gastroenterology.2017.02.002
Abstract

Little is known about the incidence of celiac disease in the general population of children in the United States. We aimed to estimate the cumulative incidence of celiac disease in adolescents born in the Denver metropolitan area.
Methods
We collected data on HLA-DR, DQ genotypes of 31,766 infants, born from 1993 through 2004 at St. Joseph’s Hospital in Denver, from the Diabetes Autoimmunity Study in the Young. Subjects with susceptibility genotypes for celiac disease and type 1 diabetes were followed for up to 20 years for development of tissue transglutaminase autoantibodies (tTGA). Outcomes were the development of celiac disease autoimmunity (CDA) or celiac disease. CDA was defined as persistence of tTGA for at least 3 months or development of celiac disease. Celiac disease was defined based on detection of Marsh 2 or greater lesions in biopsies or persistent high levels of tTGA. For each genotype, the cumulative incidence of CDA and celiac disease were determined. To estimate the cumulative incidence in the Denver general population, outcomes by each genotype were weighted according to the frequency of each of these genotypes in the general population.
Results
Of 1339 subjects followed, 66 developed CDA and met criteria for celiac disease and 46 developed only CDA. Seropositivity for tTGA resolved spontaneously, without treatment, in 21 of the 46 subjects with only CDA (46%). The estimated cumulative incidence for CDA in the Denver general population at 5, 10, and 15 years of age was 2.4%, 4.3%, and 5.1% respectively; incidence values for celiac disease were 1.6%, 2.8%, and 3.1%, respectively.
Conclusions
In a 20-year prospective study of 1339 children with genetic risk factors for celiac disease, we found the cumulative incidence of CDA and celiac disease to be high within the first 10 years. Although more than 5% of children may experience a period of CDA, not all develop celiac disease or require gluten-free diets.

TAKE-HOME MESSAGE
•A cohort of 31,766 infants underwent HLA-DR, DQ genotyping, and 1339 of them with susceptibility genotypes for celiac disease and type 1 diabetes were subsequently followed for 20 years. Celiac disease autoimmunity (CDA), defined as persistence of tissue transglutaminase autoantibodies (tTGA) for ≥3 months, was diagnosed in 46 participants; 66 developed CDA and met the criteria for celiac disease. In 21 of the 46 diagnosed with CDA only, seropositivity resolved spontaneously with no treatment. The estimated cumulative incidence for CDA in this population was 2.4% at 5 years, 4.3% at 10 years, and 5.1% at 15 years of age. The corresponding incidence values for celiac disease were 1.6%, 2.8%, and 3.1%, respectively.
•Among children with genetic risk factors for celiac disease, around 5% will develop CDA at some point but not all of these will have celiac disease or require treatment.

Key Words:
transglutaminase, disease progression, DR3-DQ2, DR4-DQ8
Abbreviations:
tTGA (tissue transglutaminase autoantibody), HLA (Human Leukocyte Antigen), CD (celiac disease), CDA (celiac disease autoimmunity)

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