Can Newer Blood Tests Replace Biopsy?
Patients and doctors would all be happy if there was a way to diagnose celiac disease without having to do an intestinal biopsy. It would also be very good to be able to rule out celiac disease in patients who don’t have it without doing a biopsy.
As blood tests have improved over the years, people working on the diagnosis of celiac disease have tried to find a test or combination of tests that can safely rule out the possibility that a person has CD without an intestinal biopsy, and also tests that can clearly indicate that a person has celiac disease without having to do an intestinal biopsy.
A “gold standard” medical test is one that is considered the absolute best way to diagnose a disease, and is presumed to always be correct. There are experts who would be reluctant to give up the intestinal biopsy as the “gold standard” test for celiac disease. However, this test is invasive and not without risk. It can also be evaluated incorrectly by pathologists who do not see a lot of cases of CD.
Besides the tests that have been in use for many years, EMA (which stands for endomysial antibodies) and a-tTG (which stands for antibodies to tissue transglutaminase), newer tests are available. The most important new test is based on finding antibodies to specific parts of gluten called gliadins. The gliadins have already been changed in people with celiac disease, and the blood test looks for antibodies to the altered gliadins, which are called deamidated gliadin-related peptides (DGPs).
The new tests look for two kinds of antibodies, both IgA and IgG at the same test. This means that the 5% of people with celiac disease who do not have IgA do not need to do additional tests. There are a number of companies making these newer tests. There are also using them in combination, usually with a-tTG.
A recent study of almost 700 adults separated the group into those people at low risk of CD, and those with high risk of CD. The patients being evaluated because of abdominal pain, weight loss, iron-deficiency anemia or other symptoms that could be from celiac disease but had not yet been tested or diagnosed were the high risk group. The low-risk group was made up of people who were going to have upper GI endoscopy for other reasons, such as heartburn. These low risk patients agreed to have their small intestine biopsied during the procedure.
All of the participants had a full panel of celiac blood tests performed. Specific labs and specific pathologists were used to do all the testing. The endpoint of the study was a diagnosis of celiac disease made by biopsy. This could be supported by positive blood tests. Reaction to a gluten-free diet was then observed if possible.
Many of the blood tests were very good at predicting celiac disease in the high-risk group. All the patients diagnosed with CD had at least one positive blood test.
The results of the blood tests were compared with the biopsies. Various formulas and cutoff values were used, attempting to find a combination that could accurately predict which patients had celiac disease.
The blood tests did not perform well in the low risk group. The best was a combination of a-tTG plus the DGP/tTG Screen. If these together were positive, there was a 99% chance that the person had celiac disease. However, over 18% of celiac cases would be missed in the low risk group.
In the high-risk group, many of the blood tests had good results. The newer combination of DGP/tTG, if positive, correctly identified 100% of the patients with celiac disease.
The researchers concluded that the new tests looking for antibodies against DGP may be very good diagnostic tests in people at high risk for celiac disease. They believe that using the DGP/tTG Screen along with another test (IgA a-tTG or IgA a-DGP) would be enough to make a positive diagnosis of celiac disease and avoid biopsy in more than 92% of high-risk patients.
No combination was this conclusive in the low risk group. It is hard to screen this group as well as hard to diagnose them even with biopsy, because biopsy results may be inconclusive or show limited damage. This raises the question of whether or not these cases are really mild celiac disease.
The authors suggest more research is necessary, but the results do indicate that a diagnosis of celiac disease in a high risk patient could be made without biopsy. While many of these tests are used now, it is probably a long way off before blood tests replaced the intestinal biopsy. They are not anywhere close to being able to rule out CD in patients at low risk of the disease.
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Bai JC. Celiac disease serology in patients with different pretest probabilities: Is biopsy avoidable? World J Gastroenterol 2010; 16(25): 3144-3152.