What Blood Tests Tell Your Doctor
The definitive diagnosis of celiac disease must be made by biopsies of the small intestine. Obtaining tissue for biopsy requires a somewhat invasive procedure. It is not a good way to screen people for celiac disease. Additionally, small bowel biopsies will only be abnormal while a person with celiac disease is still eating gluten. Blood tests can still be positive for 3 to 12 months after a person with suspected celiac disease has stopped eating gluten.
The newer blood tests for celiac disease can be very accurate when done properly. They measure certain antibodies in the blood that people with celiac disease make.
One measures the amount of antibodies in the blood to human tissue transglutaminase (tTG). Tissue transglutaminase is a key enzyme in the sequence of events leading to small intestinal damage as a result of gluten intolerance. When wheat proteins are digested, pieces of peptides remain intact, such as alpha-gliadin, which is high in proline and glutamine. These small pieces pass through the lining of the intestine and reach cells there that can react to them.
If some of the glutamine in the peptides undergoes what is called deamidation, the peptides stick more strongly to certain molecules. These are recognized by a certain kind of T cell which causes the immune response to begin. In fact, the deamidation is a key step in causing celiac disease, and it is catalyzed by an enzyme called tTG. A person with celiac disease makes antibodies against tTG, and the amount of these antibodies can be measured and used to diagnose the disease. Antibodies to tTG are usually expressed as tTGA.
There are at least three different ways to measure tTGA. The most common tests at the current time have a sensitivity of approximately 0.95 and a specificity of about 0.983 in adults. The numbers in children are 0.957 and 0.99, respectively.* This means that of 100 adults with celiac disease, the test will be positive in 95 of them. 5 patients with CD will falsely test negative. Of 100 adults without celiac disease, 98.3% will have a negative test. That means around 2 out of 100 patients without celiac disease will have a false positive test.
These results are considered very good. Tests done correctly can be used to screen for celiac disease. A high specificity is needed for a screening test, because a negative test will almost certainly mean a person does not have celiac disease. This test is also good for diagnosing CD, because a positive test is almost as certainly a true positive.
Other tests measures antibodies to the endomysium (part of the muscle cells in the intestinal lining), called endomysial antibodies, or EMA. There are a number of ways to perform this test, and they are not all equally good. When the best test is performed properly, it can be very accurate, with a sensitivity of 0.974 in adults and a specificity of 0.966, for example. Again, that would mean that of 100 adults with celiac disease, between 3 and 4 would not have a positive test. Of 100 people without celiac disease, around 3 will have a falsely positive test.
AGA or anti-gliadin antibodies were the first kind of antibodies measured as a way to check for celiac disease. The sensitivity and specificity of tests for AGA were in the range of 0.90 or 90%. That is not good enough to use as a screening test or diagnostic test, especially now that there are better blood tests.
EMA and tTGA are often both used together, to screen patients for celiac disease. Most of the patients with celiac disease will be found using these tests.
Patients with positive tests and histories consistent with celiac disease still need small bowel biopsies done to confirm the diagnosis. If your doctor thinks you might have celiac disease, he or she will probably order tTGA and/or EMA, along with general tests to get an idea of whether or not you have any vitamin or other deficiencies. This does not mean you won’t have biopsies done. To prove you have celiac disease, you would need to be eating gluten and then have the test in which biopsies of the small intestine are taken.
If you do not want to eat gluten again, or there are other reasons you do not want biopsies done, the diagnosis of celiac disease may be made based on a history that sounds like celiac disease, positive blood tests, and improvement on a gluten-free diet. The reason for the biopsies is that most doctors want to be as close to 100% positive as possible before telling someone that they need to avoid gluten for the rest of their life.
Helpful Scientific Definitions:
Sensitivity is the number of true positives divided by the number of true positives plus the number of false negatives. It is a measure that tells scientists how many of the actual cases of a disease the test picks up. 100% sensitivity means that a test finds all the actual cases of the disease.
Specificity is the number of true negatives divided by the number of true negatives plus the number of false positives. 100% specificity would mean that all the people without the disease are measured as without the disease. A high specificity indicates that people without the disease will be recognized as without the disease.