People with celiac disease who eat gluten have higher than normal levels of certain antibodies in their blood. Antibodies are produced by the immune system in response to substances that the body perceives to be threatening. Think of antibodies as soldiers instructed to fight a specific enemy, only in the case of an autoimmune disorder such as celiac disease, the enemy is actually something that is harmless for people without the disease—in this case, the proteins in wheat, rye, and barley that are generically known as “gluten.”
To help diagnose celiac disease, physicians first test blood to measure levels of certain antibodies. These antibodies are:
A positive antibody test suggests that a person might have celiac disease, but it is not a conclusive test; a biopsy will be needed to confirm the diagnosis.
Your doctor may order one or more of the antibody tests indicated above (a “panel”) to aid in diagnosis.
If antibody tests and/or symptoms suggest celiac disease, the physician needs to confirm the diagnosis by obtaining tiny pieces of tissue from the small intestine to check for damage to the villi. This is done in an endoscopic biopsy procedure. Under sedation, the physician eases a long, thin tube called an endoscope through the mouth and stomach into the small intestine, and then takes samples of the tissue using small instruments passed through the endoscope.
Even though the blood tests are quite accurate, they may occasionally produce false positive results (when someone who does not have celiac disease receives a positive test result) or, less commonly, false negative results (when a person with celiac disease receives a normal test result). Thus, biopsy of the small intestine is the only way to diagnose celiac disease.
While it is rare, it is possible for patients to have a negative antibody test results and still have celiac disease. IgA deficiency is one example where this could occur. Further medical evaluation is important for anyone who is still experiencing symptoms to establish the diagnosis or to rule out celiac disease as a part of establishing another diagnosis.
Antibody tests are accurate only when a patient is on a gluten-containing diet. Those concerned about celiac disease are strongly discouraged from starting a gluten-free diet without having had a firm diagnosis. Any change in the diet, even as briefly as a month or two, can complicate the diagnostic process.
A screening test is commonly used when an individual is in a risk group for celiac disease, whether or not he or she has symptoms. The tTGIgA test is usually the one offered for celiac screening events, as it is the most sensitive test available. In fact, it is generally believed that about 98% of people with celiac disease have a positive tTG test. While the tTG test is very specific, it also can produce false positive results on occasion. Indeed, some people with Type 1 diabetes, Hashimoto’s thyroiditis, and autoimmune liver conditions are especially likely to have elevated tTG without having celiac disease.
The gene tests are not antibodies and thus do not depend on the diet (gluten or gluten-free) that the person is on. If negative, these gene tests are very useful, as in this case where celiac disease can be confidently ruled out for life.
People with IgA deficiency require a different version of the antibody tests listed at left. The tTG and EMA tests have IgG versions and these tests will then be accurate for someone with IgA deficiency. IgA deficiency is diagnosed when a person’s total serum IgA test results are very close to zero (less than 10 mg/dL). This is not a test for celiac disease, but a means to make a more accurate diagnosis of IgA deficiency
When an individual is diagnosed with celiac disease, the entire family learns that they must be tested for the condition, for they are now at risk. First-degree relatives (parent, child, sibling) have a 1 in 22 chance of developing celiac disease in their lifetimes; in second-degree relatives (aunt, uncle, grandparent), the risk is 1 in 39. A simple genetic test can determine if further screening is needed or it can completely rule out the possibility of developing the disease. If the genetic test is positive for celiac disease, the individual should have antibody screening regularly to help determine if and when the disease is active, keeping in mind that they may well remain free of celiac disease for life.
DNA testing is available (either via blood test or a cheek swab) to determine whether or not an at-risk individual carries the genes responsible for the development of celiac disease. These genes are located on the HLA-class II complex and are called DQ2 and DQB, which in contemporary terms are named DQA1*05XX and DQB1*02XX for HLA-DQ2 and DQA1*03XX and DQB1*0302 for HLA-DQ8. Every case of celiac disease has been found to show these so-called haplotypes; therefore, a negative gene test indicates that celiac disease cannot develop in that individual.
There are two main reasons for using the genetic test when evaluating an individual for celiac disease. The first case is to “rule out” celiac disease, which is a medical term that indicates an individual does not possess a necessary risk factor for the development of celiac disease, or does not have a genetic predisposition. Without this factor, it is impossible for someone with a negative gene test to develop celiac disease in the future. People who test negative for the gene would not be required to have regular antibody screening for the remainder of their lives. Children of an adult with celiac disease should have the gene test so the parents will know which children need close monitoring.
For individuals with symptoms who have not had a biopsy to diagnose celiac disease but who have been on the gluten-free diet for a significant period of time, the gene test is often the only way to determine if symptoms could possibly be related to celiac disease. For a person who faces this situation, a negative gene test indicates that symptoms are not the result of celiac disease. A positive gene test, however, does not diagnose the disease but increases the likelihood that it is present.
The gene test does not diagnose celiac disease. It places an individual into an at-risk group for celiac disease, which indicates the individual should be closely monitored with antibody testing in the future. When the genetic predisposition for celiac disease was first detected (on Chromosome 6), researchers noted that having the genes are required for the disease to develop, but that’s not the only factor. In fact, up to one-third of the US population has the genes for celiac disease. This means that people with DQ2 or DQ8 can develop celiac disease at any time.
The blood tests that most people with celiac disease are familiar with are the antibody tests. These tests, such as the tissue transglutaminase test (tTG) or the anti-endomysial (EMA) antibody test, measure the autoimmune response triggered by gluten that occurs at a point in time. (Think of it as a photograph.) These are important tests because they characterize the extent to which the immune system is responding to gluten.
Unlike antibody testing, the HLA gene testing for celiac disease measures the presence or absence of genetically programmed molecules that are found on the surface of some cells. The HLA gene test for celiac disease can be performed at any time after birth (and even on the cord blood at birth)—an individual is born either with or without these factors and that does not change over time.
Inheriting the genes for celiac disease occurs differently than the manner in which many genetic traits are passed on. We are accustomed to thinking in terms of dominant or recessive genes, which are inherited from both parents and form sets to determine hair color, height, and other human health characteristics. In fact, even though the DQ2 and DQ8 genes are passed on similarly, having them is not sufficient to determine the occurrence of the disease, even if the genes are inherited from both parents.
Because 35% of the American population have either the DQ2 (more commonly) or DQ8 gene, it is possible for two affected people to marry each other. The genes can be passed on by males as well as females. Therefore, one person’s gene test doesn’t necessarily mean that the other side of the family is not affected as well.
Genetic testing is available through most doctors. Most of the major diagnostic labs in the United States have the capability to run HLA testing for celiac disease. Kimball Genetics, a division of LabCorp, also offers the test using a cheek swab rather than a blood sample. More and more insurance companies are covering the cost for the test, especially if the individual being tested has a risk factor for the disease.
No, the presence or absence of genetic factors is not influenced by diet for a genetic test, which is different than the antibody tests that are dependent on detecting gluten in the diet.