<<Disclaimer: Verify this information before applying it to your situation.>> New Developments in CD Research and Rectal Challenge, Dr. Michael ---------------------------------------------------- Marsh, University of Manchester Medical School, England Dr. Marsh believes it is probable that the avenins in oats are not toxic to celiacs. The regulation of the immune systems is brought about by genes. In a celiac the response is not controlled; the immune system fails the "self/non-self" test, causing an inappropriate response. The antigen is in highest concentration in the jejunum, therefore the highest number of T-cells can be found there. However, even down in the rectum some of the T-cells exist. Therefore, a rectal challenge with gluten will result in inflammation in a celiac. Dr. Marsh described the rectal gluten challenge as a diagnostic and management tool. The premise of the test is that a gluten challenge can be conducted anywhere in the intestinal tract and show a reaction. The T lymphocytes are the agents of damage, and in celiacs produce an uncontrolled response. With a biopsy after 4 hours, computer scanning, and mathematical analysis software, it is possible to separate celiacs from controls with 100% certainty. [Editor's note: There doesn't appear to be a published dispute with Dr. Marsh's findings, but there also does not appear to be a published duplication of his results from other sources.] How do we measure this response? There are three areas to consider: the surface epithelia, the crypt epithelia, and the lamina propria in between. A 100 x 100 micron area is used as the standard to compare against. Here is a comparison of the number of lymphocytes found in the 100x100 micron area: Controls Untreated CD surface epithelium 2.6 0.6 crypt epithelium 0.6 1.9 lamina propria 1.4 2.8 Loft reported the results of a study in *Gastroenterology* 1989. There were 10 subjects and 6 controls. Gluten was introduced to the rectal tissue. A biopsy afterwards showed an inflammatory response in celiacs, but not in the controls. In only 6-8 hours there was a noticeable increase in crypt epithelial lymphocytes in celiacs. Ensari (Turkey) repeated Loft's work, with additions. There were 31 celiacs and 34 controls. For this study, an untreated celiac was defined as having "flat mucosa". Signam brand gluten was used as the antigen. Biopsies were done at 0, 2, and 4 hours. At each interval they looked at gamma, delta, and various other T-cells, along with routine blood tests, fecal fat, xylose excretion, and jejunal biopsy. After 2 hours there were changes that tended to separate celiacs from non-celiacs. The sensitivity was about 70%, specificity about 80%. After 4 hours the changes were more marked. Celiacs and non-celiacs were clearly separated. Sensitivity and specificity were both 100%. This looked "embarassingly good"; they didn't "cook" the figures. Regression analysis compared with all the other potential diagnostic tests shows only the jejunal biopsy matches the 4-hour rectal gluten biopsy in specificity and sensitivity. So why use the rectal challenge? * It is relatively easy. * It uses a well-documented protocol. * It works for any age group. * It finds latent/refractory sprues. * It is a dynamic test. (All other tests are passive, 'after-the fact' tests.) Note: The rectal challenge does NOT work in patients that are on a GF diet, so it is no different from the jejunal biopsy or the blood tests in this respect. It may still be useful though if the patient has been on a GF diet for 6 months or less. Dr. Marsh then answered some questions from the floor. Q: What diseases did the controls have in your study? A: Diarrhea, iron deficiency, bone disease, etc.; all were coming to the clinic anyway. Q: Did the technician know which samples were from celiacs and which were controls prior to counting lymphocytes? A: No, she had no idea. Q: How can people in Canada get access to this test? A: Right now you probably can't. It is not in wide use in the USA or Canada. Dr. Murray responds: It is fairly new; it is not standardized between labs. Also people in general are opposed to having items inserted in their rectums. (Not all audience members agreed.) Also the studies need to be repeated and verified elsewhere.