TTG IGA Negative & Still Celiac?

Celiac disease is commonly found when a patient reports symptoms to their doctor. Simple blood tests are run. Most commonly the Tissue Transglutaminase IGA or TTG IGA test is done. The TTG IGA test often determines if further celiac testing is warranted. The reliance on the TTG IGA test to determine further celiac testing may be a bit overblown. I’ll explain.

Celiac Testing

The TTG IGA test is one of several tests run in a comprehensive celiac blood panel. Here is how Quest Diagnostics and LabCorp define the comprehensive celiac blood panel. Notice that there are several tests in the comprehensive celiac blood panel.

Both lab testing companies include immunoglobulin A total, tissue transglutaminase IGG, and IGA, anti deaminated gliadin peptide (DGP) IGA and IGG, anti-endomysial antibodies (EMA) IGA. The panels may also include genetic screening for one of the two common genetic markers for celiac disease HLA DQ2 or HLA DQ8.

Once these initial, inexpensive blood tests are run, the patient and doctor can decide on more testing. If any of the tests are positive, the patient is referred to a gastroenterologist. During the endoscopy, the doctor will take biopsies of the small intestine. This tissue sample is then evaluated under a microscope to determine if celiac disease damage is present. If present, celiac disease is diagnosed.

This comprehensive panel can also definitively diagnose celiac disease. The triple positive means 10x normal TTG IGA, positive EMA, and positive genetic screening. So, there is absolutely value in running the complete panel.

All of these tests provide a piece to the puzzle in determining whether to refer the patient for more testing. There is even a “control” test to ensure that the tests are accurate.

Gray Area

There are many tales in social media and even medical literature of patients who have negative blood tests and positive endoscopic biopsies for celiac disease. A patient could be IGA deficient. IGA deficiency is when their immune system doesn’t generate enough immunoglobulin A to create a positive for celiac tests. Those are the most common examples. But I’ve read story after story where celiac is diagnosed through a variety of methods.

Initially, a patient will talk to their GP about their issues with food and request a celiac test. The GP runs the test and finds a negative TTG IGA. Often, the GP will say they are gluten intolerant and tell them to cut out gluten or not. This is where the study comes in.

New study

April 2021 the journal Gastroenterology published a study looking at potential verification bias of the TTG IGA test.

Before the study, the TTG IGA test was thought to be 92% sensitive and 95% specific to celiac disease. The sensitivity of a test indicates how often the test can correctly identify someone WITH the disease. The specificity of the test indicates how often the test can correctly identify someone WITHOUT the disease. The TTG IGA was thought to be a really, really good test.

The sensitivity of the TTG IGA may be overestimated. The researchers say that the sensitivity of the TTG IGA may be as low as 57%. Scientists postulate that because someone with a positive TTG IGA is often referred for a endoscopy. Someone with negative TTG IGA is not often referred for an endoscopy creating the potential for verification bias.

My take

Is this confirmation bias possible? Maybe. Do I think it lowers the sensitivity of the TTG IGA to a little better than 50/50? No.

The TTG IGA should not be evaluated in isolation. The panel can be looked at as a whole before a confirmation endoscopy is performed. The comprehensive panel should be run. Running the comprehensive panel ensures multiple data points. Making it easier to determine if a referral should be made. Very few diseases are diagnosed by a single test at a single point in time. Much of the time many data points, including blood tests, diagnostic tests, and patient symptoms are gathered to ensure a proper diagnosis. Diagnosing celiac disease should be no different.

Leave a Reply