Q: I am a 42 years old female. Everyone in my family tested negative for IgA-tTG but is symptom free, except for one who has positive IgA-tTG and also symptom free. No other tests have been done. All decline endoscopy with biopsy. Would genetic testing be of value and for whom? Does IgA-tTg test for entities other than Celiac disease? Is blood, cheek tissue, or stool best for Celiac disease? Can Celiac disease and genetic testing all be done on one specimen?

A:Celiac disease or sprue or gluten-sensitive enteropathy is an autoimmune disease affecting the gastro-intestinal tract in which individuals have a permanent intolerance to certain proteins found in cereals like wheat, rye, barley etc. It occurs in genetically susceptible individuals and antibodies are formed against transglutaminase (tTG). The protein gluten triggers the immune reaction. The disease has a highly specific association with two human leukocyte antigens (HLA) DR17-DQ2 and DR4-DQ8. The prevalence of the condition in first degree relatives (parent, child, sibling) is about 5-10% and in second degree relatives, (aunt, uncle, cousin, grandparent) about 3%. Screening for the disease is done by testing the blood for antibodies directed against tTG by ELISA technique and the test has a high sensitivity and specificity. If a person has been on a gluten-free diet for long (6 months to a year), the antibodies may become undetectable in the blood. The current guidelines recommend that this test be followed by a duodenal biopsy (with at least 4 samples being taken) to confirm the diagnosis. If a family member is diagnosed to be suffering from the disease, other members require regular antibody testing (lifetime screening) as the disease can occur at any age. Genetic test determines if an at-risk individual (due to family history of disease) carries the genes responsible for the disease. If the genes are absent, the person will never develop the disease and they do not require regular antibody screening test. In case one tests positive for the genes, it places the individual in ‘at-risk’ category and regular monitoring would be required. Genetic test may also be required in those who have symptoms but have not had a biopsy as in this case, a negative test would mean that the disease is not present and symptoms are due to some other disorder. The presence of the genes, however, does not mean that you have celiac disease; it only labels you ‘at-risk’ or genetically predisposed and you would require regular antibody testing. Nearly 33% of the U.S. population carries these genes but only 1 to 4% of them go on to develop the disorder. Both the antobody test and the genetic test are done on a blood specimen and can be done together. You need to contact your doctor or laboratory for further details as often the antibody testing is done in a Clinical Chemistry/Biochemistry lab while HLA is tested in a Genetic laboratory.