the patient celiac

The Alphabet Soup of Celiac Blood Testing

0 comments May 09, 2017

Disclaimer: I am proud of myself for even attempting to write this post as I cried when I started reading my immunology textbook as a first year medical student.
What does TTG mean?

TTG is the abbreviation for tissue transglutaminase, an enzyme that is present in the intestines, as well as in other parts of the body. Enzymes are involved in the bodies’ biochemical reactions.

In celiac disease the immune system produces antibodies that attack TTG when gluten is eaten—this is an “autoimmune” response as the antibodies that are made attack one’s own tissues (differs significantly from the immune response in a food allergy in which antibodies are produced against specific food proteins).  Anti-TTG antibody levels are elevated in active, untreated celiac disease.

There are 2 main types of anti-TTG antibodies, or immunoglobulins, that can be measured when one is tested for celiac disease: TTG IgA and TTG IgG.  In general the IgG type are found throughout the body and are often used in testing for bacterial and viral infections, while the IgA type are prevalent in mucosal surfaces such as the respiratory and gastrointestinal tracts. Of note, about 1-3 percent of the general population, including those with celiac, are deficient in serum IgA (so cannot make any IgA antibodies, including the TTG IgA antibodies of celiac disease).

Serum TTG-IgA antibodies are positive in approximately 95% of celiacs who are on gluten-containing diets. However, celiac disease blood testing should always include a TTG IgA as well as a serum IgA. This is because TTG IgA levels will not rise if one has both celiac disease and a serum IgA deficiency (as described above). In these cases it can be useful to obtain a serum TTG-IgG level to help figure out whether celiac disease is present. But, the TTG-IgG is not as specific as the TTG-IgA  for celiac disease, and in a recent study many subjects with a normal serum TTG IgA but elevated TTG IgG did not actually have celiac disease.  According to the University of Chicago Celiac Disease Center there are other diseases that can cause elevated TTG antibodies, including Type 1 diabetes, Hashimoto’s thyroiditis, inflammatory bowel disease, and autoimmune liver disease.

What about DGP?

DGP stands for deamidated gliadin peptide. Gliadin is one of the two main proteins in gluten. The tissue transglutaminase enzyme, which we discussed earlier, changes gliadin proteins into deamidated gliadin peptides (DGPs) through a chemical reaction. These peptides stimulate both of the main branches of the immune system and DGP IgA and IgG antibodies are created.  Research over the last few years has shown that DGP-IgA and IgG levels are usually elevated in celiac disease,  that these antibodies might rise earlier than the TTG antibodies do, and that the DGP-IgG might be a better test for celiac than the TTG-IgG in the setting of serum IgA deficiency. There is also literature showing that the DGP tests may be of benefit in the pediatric population (you can see my previous post about DGP antibodies for more information on its use in children).

HMGB1 stands for High Mobility Group Box 1, a cytokine (small protein) that is produced by the immune system and can cause inflammation.  A recent Italian study showed that HMGB1 levels are significantly higher in children with celiac disease than controls and that the levels of HMGB1 correlate with intestinal damage. This may end up being a useful tool to be able to track the progress of small bowel healing after celiac diagnosis and the initiation of the gluten free die in both children and adults.

Important Points:

-If a patient with celiac disease has already been on a gluten-free diet when celiac blood tests are done, the tests will be falsely negative. At the present time the only way for one to be diagnosed in this situation is to start a "gluten challenge" in which gluten is eaten everyday for weeks to months prior to blood testing.

-It is possible to have normal celiac antibodies in the setting of celiac disease. This is called "seronegative" celiac disease and can occur in up to 10% of people with celiac disease. This is why it is important to have a small bowel biopsy if there is still a concern for celiac disease in the setting of "normal" blood tests.

-Children under the age of 3 to 4 may not have elevated TTG or DGP antibodies, even if celiac disease is present. An endoscopy with small bowel bopsy is often needed in this age group for a firm diagnosis of celiac.


Absah, I., Rishi, A., Gebrail, R., et al. Lack of utility of anti-tTG IgG to diagnose celiac disease when anti-tTG IgA is negative. Journal of Pediatric Gastroenterology and Nutrition. 64(5): 726-729.

Lammi AArikoski PSimell S,et al. Antibodies to deamidated gliadin peptide in diagnosis of celiac disease in children. J Pediatr Gastroenterol Nutr. 2015 May; 60(5):626-31.


Manti, S., Cuppari, C., Tardino, L, et al. HMGB1 as a new biomarker of celiac disease in children: a multicenter study.  Nutrition. May 2017. 37:18-21.



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