Celiac disease, also known as gluten sensitive enteropathy is very common but frequently missed. It is a autoimmune disease of intestinal damage due to gluten in people who are genetically predisposed. Classic Celiac disease is diagnosed by abnormal blood tests and an abnormal appearing intestine on biopsy and symptoms that resolve with gluten free diet.

Several blood tests exist for Celiac disease. They have varying degrees of accuracy. Some are more sensitive, meaning they will be positive in milder forms of the disease but are not specific, meaning a positive test may not indicate Celiac disease. Others are felt to be very specific, meaning that when they are positive, it is almost certain you have the disease.

The most specific tests are tests for Celiac disease endomysial antibodies (EMA) and tissue transglutaminase sntibody (tTG) antibody tests. These two tests are IgA based tests and can be negative if you are deficient in the immunoglobin IgA, which occurs in 10-20% of people with Celiac. When either EMA or tTG are positive Celiac disease is very likely and usually the intestine biopsy is positive. Recent studies indicate that the tTG may only be positive in 40% of true Celiacs when mild degrees of intestine damage are present on biopsy. Seronegative Celiac, meaning the blood tests are negative but the biopsy is positive may occur in up to 20% of Celiacs.

Antibodies for gliadin (AGA), the toxic fraction of gluten are considered very sensitive but not specific for Celiac disease. Newer assays for AGA antibodies for gluten that has undergone a chemical change called deamidation appear to be more specific for Celiac disease (Gliadin II, Inova) than the older gliadin tests. They also may be as or more accurate than EMA and tTG antibody tests but are not yet widely available.

The most distressing problem for people with lesser forms of gluten intolerance who have blood tests and/or biopsies that are normal or borderline yet respond to a gluten free diet is either not be taking seriously or knowing for sure if they are sensitive to gluten. For these individuals stool antibody testing for antigliadin and tTG have been helpful. Such stool testing has been performed in research labs and published in a few studies but only recently available through the commercial lab, Enterolab. Founded by a former Baylor research gastroenterologist, Dr Ken Fine, the tests are available to order by people online without a doctors order but are not generally covered by insurance. Dr. Fine, who patented the test, has yet to publish the results of his findings in a peer reviewed journal so his tests are not widely accepted. However, his unpublished data and clinical experience of some of us who have used his test have indicated the tests are very sensitive for signs of gluten sensitivity. He reports that they are 100% sensitive for Celiac disease and highly sensitive for gluten sensitivity of lesser degrees. In the presence of symptoms that reverse on a gluten-free diet abnormal stool antibody levels can be found in most people before blood tests or biopsies become abnormal.

Small intestine biopsies during upper gastrointestinal endoscopy are considered the “gold standard” for the diagnosis of Celiac disease. However, recent studies have demonstrated that some people with gluten sensitivity, especially relatives of Celiacs with little or no symptoms, have changes from gluten injury to the intestine that can't be seen with normal microscope examination. They can only be seen with special stains not routinely done or with a research electron microscope. The special stains are known as immunohistochemistry stains. They stain specialized white blood cells called lymphocytes in the intestinal lining tips or villi. When these lymphocytes are increased it is known as intraepithelial lymphocytosis or increased IELs and it is the earliest sign of gluten induced injury or irritation. Electron microscopy also reveals very early ultrastructural changes in some individuals when blood tests and standard biopsy exmination are normal. When people who have these changes are offered the option of gluten-free diet they usually responded favorably. In contrast, those who continued to eat gluten often later developed classic Celiac disease.

What these studies suggest is that a “normal small intestine biopsy” may exclude Celiac disease as defined by strict criteria but it is not a gold standard for detecting gluten sensitivity. This fact is appreciated by many individuals who have respond to a gluten-free diet they start based on their symptoms, family history, suggestive blood test or stool antibody test(s).

Another source of confusion is in the genetics of Celiac and gluten sensitivity. Testing for specific blood type patterns on white blood cells known as HLA DQ2 and DQ8 is increasingly be employed to determine if a person carries either of the two gene pattern present in 95-98% of Celiacs and predisposing to development of Celiac disease. Some use the absence of these two patterns as a way of excluding the possibility of Celiac disease and the need for testing or gluten-free diet. However, there are rare reports of documented Celiac disease in people who are DQ2 and DQ8 negative. Moreover, recent studies indicate other DQ patterns may be associated with gluten sensitivity though unlikely to predispose to classic Celiac disease.

Testing for all the DQ patterns is advocated by Dr. Fine, based on his experience with stool antibody test results. He reports the other DQ types are associated with elevated levels of gliadin and tTG in the stool and symptoms that respond to a gluten-free diet. According to his unpublished data, all the DQ types except DQ4 are associated with a risk of intolerance to gluten. Therefore, testing for all the DQ types allows a person to determine if they carrry one of the two high risk gene types for Celiac disease or the any of the other "minor DQ" genes Fine has found associated with gluten sensitivity.

Enterolab's stool testing for gliadin antibodies and tissue transglutaminase antibodies though not widely accepted, have gained favor in the lay public’s opinion as an option for determining sensitivity to gluten either despite of negative blood tests and/or biopsies or in place of the more invasive tests. Most doctors still recommend the accepted blood tests and small bowel biopsy for confirmation of Celiac. Though the reports in the lay community are overwhelmingly positive they have not been subjected to peer review in the medical community pending Dr. Fine publishing his data or other researchers reproducing his results.

However, doctors open to the broader problem of gluten sensitivity are reporting these tests helpful in many patients suspected of gluten intolerance. Especially when someone has symptoms consistent with gluten sensitivity but has negative or inconclusive blood tests and/or biopsies these tests may be very helpful though some are not certain how to interpret the tests. The national Celiac organizations are uncertain about how to comment on their application without published research though a recent article in the British Medical Journal did show stool tests highly specific for Celiac. Dr. Fine's has publicly commented that his unpublished data demonstrates those with abnormal stool tests indicating gluten sensitivity overwhelmingly respond favorably to a gluten free diet with improvement of symptoms and general quality of life.

Another problem is that there is not universally agreed upon definitions for gluten sensitivity or intolerance. This becomes specially difficult for those who do not meet strict criteria for Celiac disease yet may have abnormal tests and/or symptoms that respond to gluten-free diet. Those individuals become confused when they try to find information but don't have a formal diagnosis of Celiac disease. Consensus in the medical community on definitions and more research in this area is greatly needed.