Positive Predictive Value of Tissue Transglutaminase IgA for Celiac Disease

Celiac.com 09/19/2025 - Celiac disease is an autoimmune condition in which the immune system reacts to gluten, a protein found in wheat, barley, and rye. This reaction damages the small intestine, leading to a variety of symptoms and long-term health risks if untreated. Traditionally, diagnosis has required a biopsy of the small intestine. However, newer European guidelines allow doctors to diagnose some children without a biopsy if certain blood test results are high enough. This approach has not been widely adopted in North America. This study looked at how well one of the most common blood tests, tissue transglutaminase immunoglobulin A (tTG IgA), predicts celiac disease in children in North America.

Purpose of the Study

The main goal was to see whether high tTG IgA test results alone are reliable enough to confirm celiac disease without needing a biopsy. Researchers also wanted to see if very high results (ten times or more above the normal limit) are more trustworthy. They compared results from multiple laboratories across North America to see how consistent the tests were.

How the Study Was Done

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The study reviewed medical records from multiple centers in North America. It included children under the age of 18 who had an elevated tTG IgA blood test and who had an upper endoscopy with biopsy of the small intestine within six months of the test. A diagnosis of celiac disease was confirmed if the biopsy showed two key findings: an increase in certain immune cells within the lining of the intestine (intraepithelial lymphocytosis) and damage to the tiny finger-like projections (villous atrophy) that help absorb nutrients.

Study Population

A total of 4,019 children were included. About two-thirds were female. Nine percent had type 1 diabetes, and two percent had Down syndrome. These groups were studied separately because they are known to have a higher risk of celiac disease and sometimes show different test patterns.

Main Findings

When looking at all children with an elevated tTG IgA result, about 83 percent actually had biopsy-confirmed celiac disease. This means that roughly 17 percent of children with an elevated test did not have celiac disease based on the biopsy. When the tTG IgA level was at least ten times higher than the upper limit of normal, the accuracy improved. In this group, about 95 percent had celiac disease confirmed by biopsy. Still, 5 percent did not, and about 2 percent had a completely normal biopsy. The accuracy of the test was not the same across all laboratories. Some tests had a predictive value as low as about 72 percent, while others reached close to 89 percent for general elevated results. For the highest results (ten times the normal limit), accuracy ranged from about 89 percent to 97 percent. Children with type 1 diabetes showed slightly lower accuracy for the highest test results, with about 89 percent confirmed on biopsy.

What the Results Mean

The study shows that while a very high tTG IgA level is a strong indicator of celiac disease, it is not perfect. Some children with high results did not have the disease. The variation between laboratories means that the reliability of the test depends partly on which specific test was used. Because of these uncertainties, the authors recommend that families should not start a gluten-free diet based solely on a positive blood test. A specialist should confirm the diagnosis before dietary changes are made, ideally through a biopsy.

Why This Matters for People with Celiac Disease

For people who have celiac disease or are being evaluated for it, this study is important because it highlights both the strengths and the limits of blood testing. High tTG IgA results can strongly suggest celiac disease, especially when very high, but they do not give complete certainty. A confirmed diagnosis is critical because starting a gluten-free diet before proper testing can make it much harder to confirm the disease later. This is especially important for children, as a lifelong gluten-free diet has social, emotional, and nutritional impacts. The findings suggest that, in North America, blood tests alone are not yet reliable enough to replace the biopsy for most children. However, they also show that extremely high results are highly predictive, which could guide future changes to diagnostic guidelines.

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