High Tissue-Transglutaminase Antibody Titer Can Lead to Celiac Disease

High tTGA titer, female sex, hypothyroidism, and history of autoimmune disease are significant predictors for a diagnosis of celiac disease in adults.

High tissue-transglutaminase antibody (tTGA) titer, female sex, hypothyroidism, and history of autoimmune disease are significant predictors for a diagnosis of celiac disease (CD) in adults, according to a study published in Gastroenterology.

Although CD can develop at any age, outcomes of adults with positive results from serologic tests for tTGA without endoscopic determination of CD (called celiac autoimmunity) have not been thoroughly evaluated.

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In this prospective cohort study, researchers analyzed waste blood samples for tTGA and endomysial antibody (if titers were >2 U/mL) from adults at a community clinic (N=15,551). Testing for CD autoimmunity occurred at 2 time points, with a median interval of 8.8 years. For the purpose of this study, CD serologic status was categorized as tTGA titers <4.0 U/mL being negative, tTGA ≥4 U/mL as positive; and tTGA titers ≥40 U/mL as strong positive.

At the first time point, 15,398 of the tested samples were negative for tTGA, and only 0.32% of these showed a positive result upon second testing (n=49). Of those who were tTGA-positive at the first time point (n=153), 20% had a subsequent diagnosis of CD (n=31), 53% remained positive for tTGA without clinical diagnosis of CD (n=81), and 27% tested negative for tTGA at the second time point (n=41).

Limitations of this study included potential selection bias because serum samples were obtained from adults who were accessing health care. This could result in overestimation of new-onset rates in nonselected populations. Alternately, the prevalence of CD autoimmunity could have been underestimated because total IgA levels were not assessed. Additional limitations included a larger number of women in the retest group. The overall age of the retest group was also higher. Adults with seroconversion may also have had a high-negative or indeterminate serum status, which may suggest the necessity of follow-up in the subset of high-negative results or in an equivocal range of tTGA to detect CD. Also, some new cases of CD may have been due to a time effect.

“Our large study is of adults with diseases and conditions from a community that has a long history of epidemiology studies,” the researchers concluded. “We found that the subsequent risk of clinical CD is much greater in those who are seropositive, even though our data demonstrates that de novo CD autoimmunity can occur in adults with a prior sero-negative result.

The researchers concluded that CD immunity can occur de novo in adulthood but at a low rate. The discovered that new-onset CD was rare and systematic retesting may not be necessary (within 10 years) in persons with previously negative celiac serologic results. Furthermore, a subset of adults with positive CD serology can have spontaneous normalization of CD serologic results for no clear reason, particularly those with low initial titers of tTGA. “It may be unnecessary to retest adults who have negative serologic results unless they have high risk factors such as a family history of CD or autoimmune disease.”

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author’s disclosures.


Choung RS, Khaleghi S, Cartee AK, et al. Community-based study of celiac disease autoimmunity progression in adults [published online September 24, 2019]. Gastroenterology. doi: 10.1053/j.gastro.2019.09.006