DNA

Celiac Disease Autoimmunity

I first came across the term “celiac disease autoimmunity” a few weeks ago as I read summaries of the article “Risk of Pediatric Celiac Disease According to HLA Haplotype and Country” that was published in the July 3, 2014 issue of the New England Journal of Medicine (NEJM).

Based on my reading and interpretation of the article, it seems that celiac disease autoimmunity is interchangeable with the more commonly used term “potential celiac disease.” Both are used to describe cases in which people have abnormally high levels of celiac antibodies (TTG IgA)  in their blood but their small intestinal biopsies do not show changes consistent with celiac disease. In other words, there is an autoimmune response to gluten that has yet to cause destruction to the villi of the small intestine. For the sake of this study, the subjects had to have abnormally high TTG IgA levels on 2 separate occasions, at least 3 months apart, to be labeled as having celiac disease autoimmunity.

The results published in NEJM come from the multinational TEDDY study, which is prospectively following a large cohort of children who are at genetically at risk of developing Type 1 (juvenile) diabetes mellitus.  Since some children with both Type 1 diabetes and celiac disease share the same “at-risk” genes, HLA-DQ2 and DQ8, the researchers have also been able to follow a large group of genetically-susceptible children for the development of celiac disease. The study is ongoing and subjects are being followed for the development of both diabetes and celiac disease from infancy until age 15. This is one of many papers that have already come from the TEDDY study.

Thus far, 6403 study subjects have been found to have genes that predispose to celiac disease.  Subjects have been placed into 4 risk groups:

-HLA DQ2/HLA DQ2 (homozygous for DQ2)

-HLA DQ2/HLA DQ8

-HLA DQ8/HLA DQ8 (homozygous for DQ8)

-HLA DQ8/HLA DQ4

As you can see, the first 3 groups of kids all have 2 copies of celiac-risk genes, and the 4th group has only one copy of DQ8, so only one gene associated with celiac disease. Subjects’ testing for celiac disease autoimmunity started at age 24 months and has been repeated every year. In all, 786 of the 6403 (11%) at risk subjects were found to have celiac disease autoimmunity (elevated blood TTG IgA antibodies at least twice) at time of data analysis Overall, 25% of the children with celiac disease autoimmunity had a diagnosis of celiac disease by age 3.

The researchers broke down the risk of both celiac disease autoimmunity and celiac disease by genes and found the following risks by age 5:

Celiac Disease Autoimmunity Risk in Children with Celiac Genes by Age 5:

HLA DQ2/HLA DQ2 (homozygous for DQ2): 26%

HLA DQ2/HLA DQ8: 11%

HLA DQ8/HLA DQ8 (homozygous for DQ8): 8%

HLA DQ8/HLA DQ4: 3%

Celiac Disease Risk in Children with Celiac Genes by Age 5:

HLA DQ2/HLA DQ2 (homozygous for DQ2): 11%

HLA DQ2/HLA DQ8: 3%

HLA DQ8/HLA DQ8 (homozygous for DQ8): 3%

HLA DQ8/HLA DQ4: less than 1%

Children with both celiac disease and celiac disease autoimmunity were found to be at a higher risk of having diabetes than the general population (1% for celiac disease autoimmunity and 2% for celiac disease v. 0.3% risk for general U.S. population).

In summary, in this large study, over 25% of children with the DQ2/DQ2 genotype were found to have celiac disease autoimmunity by age 5 and greater than 10% with DQ2/DQ2 were diagnosed with celiac disease by age 5.  Over half of these children had no symptoms of celiac disease, therefore, there is a good chance that many of these diagnoses would have been missed if these children had not been subjects in this study.

After reading this article I am a much stronger proponent of genetic testing of children at risk for celiac disease, if possible. And, as my husband and I both carry genes associated with celiac disease, I feel much less guilty for making my own kids get screened for celiac disease, via TTG IgA blood testing, every 2 years (you can see my post from May 2014 for more details). Lastly, I feel much more at peace for making my at-risk youngest go through having an endoscopy and small bowel biopsy earlier this summer. The statistics from this study are definitely eye-opening.

Reference: Liu E, Lee HS, Aronsson CA, et al. TEDDY Study Group. Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med. 2014 Jul 3;371(1):42-9.

Also, if you are a research geek like I am, here are some other interesting findings from the TEDDY study thus far (found via a Pubmed.gov search):

  • The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children.
  • Between 15% and 20% of the infants in the study were introduced to solid foods before the age of 4 months.
  • The median age of early-onset diabetes is at 2.3 years. 33% of the subjects with an early diagnosis of diabetes had no symptoms of diabetes.
  • Findings have not supported the presence of viremia (recent viral infection) around the time of seroconversion in young children with rapid-onset type 1 diabetes.

4 thoughts on “Celiac Disease Autoimmunity

  1. Erica

    Jess:
    Again, it is impossible to express how much your posts help in understanding all of this.
    One question that I have that will probably start a flood of additional questions on my part: Do these findings apply only to positive TtG IgA or would it apply to peptide serology too? Specifically positive DGP IgG. And are any of these findings applicable to adults? I guess that is technically two questions. I have such a complicated situation with *all* of my testing that it does not help figure out how to proceed with potential testing as far as my two boys are concerned. It sounds like I fall into this “celiac disease autoimmunity” category but since the study was on children I don’t know.

    1. Jess Post author

      Hi Erica,
      It’s good to hear from you.
      If my interpretation of celiac disease autoimmunity and potential celiac disease being interchangeable is right, then yes, I believe that this phenomenon can also occur in adults (as potential celiac disease has been described in the medical literature in adults). Do you know if you are DQ2 and/or DQ8 positive?
      Also, here are some interesting tidbits that I just found on the Q&A section of the Univ of Chicago Celiac site, not sure if you’ve seen them or not –one refers to potential celiac but alludes only to TTG and EMA antibodies, and the other is in regards to DGP, but not in the setting of potential–but both make me think that a person in your situation should be GF!

      What are the chances of having a high tTG and a negative biopsy—even though I have a child who was biopsy-diagnosed with celiac—and still being negative for the disease?

      It’s possible to be truly negative with these facts, especially if the tTG are only mildly elevated. Also check the more specific EMA test. If it’s positive, we would conclude you’re a potential celiac, which means the disease is simply waiting to explode, and we’d suggest a gluten-free diet

      and,

      How much exposure to gluten does it take for DGP to become elevated and how long before it will return to normal?

      There is no general rule that applies to all, but we learn from each patient. That said, typically DGP are more sensitive to gluten than tTG, so they become elevated before tTG and disappear sooner than tTG once on a gluten-free diet

      Hope this helps!

      Jess

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