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News

Risk of pediatric celiac disease depends on HLA haplotype and country

A study in this week's publication of the New England Journal of Medicine evaluates children with HLA haplotype DR3DQ2 or DR4DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden.

News image

The presence of HLA haplotype DR3DQ2 or DR4DQ8 is associated with an increased risk of celiac disease.

In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).

Dr Edwin Liu and colleagues studied 6403 children with HLA haplotype DR3DQ2 or DR4DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden.

The team's primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart.

The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies.

The research team's median follow-up was 60 months.

Celiac disease autoimmunity developed in 12% of children
New England Journal of Medicine

Celiac disease autoimmunity developed in 12% of children.

Of the 350 children who underwent biopsy, 291 had confirmed celiac disease.

The team found that an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies.

The research team observed that the risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3DQ2 haplotype, and 26% and 11%, respectively, among those with two copies.

In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 among heterozygotes, and 5.70 among homozygotes, as compared with children who had the lowest-risk genotypes.

The team noted that residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity.

Dr Liu's team concludes, "Children with the HLA haplotype DR3DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood."

"The higher risk in Sweden than in other countries highlights the importance of studying environmental factors associated with celiac disease."

N Engl J Med 2014; 371:42-49
07 July 2014

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