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Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 09/25/2008 - Mucosal inflammation of the small intestine, coupled with damage to intestinal villi, is a classic indication of celiac disease. Recently, doctors have begun to embrace the idea that some patients with positive celiac blood tests may have mucosal lesions that are too small to appear on routine histopathological analysis. In the first study of its kind, a team of researchers based in Ireland set out to analyze enterocyte morphology and cytoskeletal structures using a high content analysis technology. The research team was made up of doctors Bashir M. Mohamed, Conleth Feighery, Yvonne Williams, Anthony Davies, Dermot Kelleher, Yuri Volkov, Jacinta Kelly and Mohamed Abuzakouk. The team examined duodenal biopsies from 14 untreated and 10 treated celiac patients and from 20 non-celiac control subjects. They also investigated tissue sections from six study group subjects before and after the development of gluten-sensitive enteropathy. The research team used an anti-Î±-tubulin antibody to conduct immunohistochemical studies on paraffin-embedded tissue sections. They found important differences in enterocyte morphology and intracellular cytoskeletal structures in the patients with proven celiac disease and those in the study group. Moreover, the team observed that these changes existed in the study group prior to any indication of enteropathy, as determined by standard microscopy. This is the first time researchers have used high content analysis to show specific details of enterocyte morphology. Such an approach permits doctors to quantitatively analyze enterocyte intracellular structure from standard biopsy samples and allows for detection of minute changes that develop before the classic histological lesion. This process could become important for improving the diagnosis of celiac disease. If doctors can spot celiac-related intestinal lesions before they develop, they can begin to prevent celiac disease before it develops and thereby save lives. Central European Journal of Biology Volume 3, Number 3 / September, 2008
Small Intestinal Intraepithelial Gamma/Delta T-Lymphocytes Occur Inversely to Lymphomas in Refractory Celiac Disease
Jefferson Adams posted an article in Cancer, Lymphoma and Celiac DiseaseCeliac.com 01/20/2009 - Refractory celiac disease is a serious condition that occurs when celiac symptoms and intestinal damage continue even when the patient consumes a gluten-free diet. There are two types of refractory celiac disease (RCD). In RCD type I, immuno-phenotype of intraepithelial lymphocytes (IELs) are normal and polyclonal, while RCD) type II, is noted for the presence of an abnormal intraepithelial lymphocyte (IEL) population (CD7+ CD3âˆ’ CD4/8-cytoplasmic CD3+). More than half of people with this condition develop enteropathy-associated T-cell lymphoma (EATL), a rare but virulent form of cancer with high mortality rates. A team of doctors recently set out to examine the relationship between lymphoma development and intraepithelial gamma/delta T-lymphocytes in the small intestine of patients with all types of celiac disease, as compared to the general population. The team was made up of Wieke H.M. Verbeek, M.D., B. Mary E. von Blomberg, Ph.D., Petra E.T. Scholten, B.Sc., D. Joop Kuik, M.Sc., Chris J.J. Mulder, M.D. Ph.D., and Marco W.J. Schreurs, Ph.D., all from Amsterdam’s VU University Medical Center. A certain type of IELs called TCRÎ³/Î´+ IELs may play an important role in repairing mucosa, maintaining homeostasis, and guarding against tumor development. TCRÎ³/Î´+ IELs in the human intestine have recently shown promise in the regulation of uncomplicated celiac disease. In the study, the research team wanted to see if patients with RCD II had fewer TCRÎ³/Î´+ IELs than either RDC I, or celiac disease, an thus provide a possible explanation for ongoing mucosal damage and inflammation, and the development of abnormal T cells that tend to morph into EATL. The team used a method called multi-parameter flow cytometric immuno-phenotyping on IELs obtained from recent small bowel biopsy specimens from a fairly large, distinct celiac disease and control groups (N = 87). Patients with RCD II showed a much lower ratio of TCRÎ³ Î´+ IELs compared to either RCD I or celiac disease patients. Whereas, patients with uncomplicated celiac disease showed significantly higher numbers of TCRÎ³ Î´+ IELs than were found in the control group. The results showed the relationship between TCRÎ³ Î´+ IELs and aberrant IELs to be negative. It is interesting to note that TCRÎ³ Î´+ IELs numbers do rise in RCD II patients after effective treatment. The negative relationship between TCRÎ³ Î´+ and abnormal IELs, together with their known role in regulating uncomplicated celiac disease, suggests that TCRÎ³ Î´+ IELs may play a crucial role in helping the body to repair mucosa, maintain homeostasis and possibly even guard against tumor development. These cells may serve as important markers, along with the abnormal T cells, to help distinguish between types of celiac disease, and to gage the effectiveness of treatment efforts. Am J Gastroenterol 2008;103:3152–3158