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Higher Celiac Disease Risk in Children with Certain HLA Haplotypes

Celiac.com 07/21/2014 - The presence of HLA haplotype DR3–DQ2 or DR4–DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).

Photo: CC--Phalinn OoiA research team recently set out to determine the risk of celiac disease autoimmunity and celiac disease, by age and by halpotype, in children. The research team included Edwin Liu, M.D., Hye-Seung Lee, Ph.D., Carin A. Aronsson, M.Sc., William A. Hagopian, M.D., Ph.D., Sibylle Koletzko, M.D., Ph.D., Marian J. Rewers, M.D., M.P.H., George S. Eisenbarth, M.D., Ph.D., Polly J. Bingley, M.D., Ezio Bonifacio, Ph.D., Ville Simell, M.Sc., and Daniel Agardh, M.D., Ph.D. for the TEDDY Study Group.

The team studied 6403 children with HLA haplotype DR3–DQ2 or DR4–DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The study’s primary end point was the development of celiac disease autoimmunity, which the team 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 itself, which they defined as either a diagnosis on biopsy or persistently high levels of tTG antibodies.

The average follow-up was 5 years, with an overall range of 46 to 77 months. A total of 786 children (12%) developed celiac disease autoimmunity. A total of 350 children underwent biopsy, and 291 of those were diagnosed with celiac disease. Another 21 children did not undergo biopsy, but showed persistently high levels of tTG antibodies.

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For children with a single DR3–DQ2 haplotype, rates of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively. For those with two copies (DR3–DQ2 homozygosity) rates of celiac disease autoimmunity and celiac disease by the age of 5 years were 26% and 11%, respectively.

The adjusted hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among children with one gene, and 5.70 (95% CI, 4.66 to 6.97) among children with both genes, as compared with children who had the lowest-risk genotypes (DR4–DQ8 heterozygotes or homozygotes).

Living in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25). Children with the HLA haplotype DR3–DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood.

People in Sweden face a higher risk for celiac disease autoimmunity and celiac disease than residents of other countries. These finding highlight the importance of studying environmental factors associated with celiac disease.

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Recently diagnosed last week does the pain ever get better??

George, i am sorry that you are not feeling well! ?? I am not a doctor, but just trying out drugs to stop your symptoms just seems like a band aid approach. It sounds like he suspects IBS which is really, in my opinion, "I be stumped". Has inflammatory bowel disorder (IBD) (more lovely autoimmune disorders) been ruled out? This includes both Crohn's and Colitis. My niece was diagnosed with Crohn's finally with a pill camera after all other tests were given. The damage was not within reach of any scope. I am just throwing out suggestions. Hopefully, you and your doctor will figure it out soon!

Celiac disease is an autoimmune disease that happens to have a known trigger -- gluten. Flare-ups develop (antibodies) causing damage. Not just in the small intestine, but systemically. One gluten exposure can cause antibodies to increase for days or months! Antibodies are being measured during the celiac blood tests. If there is no gluten exposure, there will be no antibodies. These antibodies can come down in some people in as little as two weeks. Recommendations require gluten 2 to 4 weeks daily for the biopsies taken via endoscopy in order to be sure to catch damage, but 8 to 12 weeks for the blood tests. The endoscopy is considered the "gold standard" in helping to diagnose celiac disease, but there are other things that can damage the small intestine. So, the blood test helps solidify the diagnosis. So, if you want a good result on your endoscopy, you need to be eating gluten daily for two week prior at a minimum. I know it is tough and you are feeling sick. Wish there was a better way to catch active celiac disease.

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