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Small Intestinal Intraepithelial Gamma/Delta T-Lymphocytes Occur Inversely to Lymphomas in Refractory Celiac Disease

Celiac.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+ CD3− 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 TCRγ/δ+ IELs may play an important role in repairing mucosa, maintaining homeostasis, and guarding against tumor development. TCRγ/δ+ IELs in the human intestine have recently shown promise in the regulation of uncomplicated celiac disease.

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In the study, the research team wanted to see if patients with RCD II had fewer TCRγ/δ+ 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 TCRγ δ+ IELs compared to either RCD I or celiac disease patients. Whereas, patients with uncomplicated celiac disease showed significantly higher numbers of TCRγ δ+ IELs than were found in the control group. The results showed the relationship between TCRγ δ+ IELs and aberrant IELs to be negative. It is interesting to note that TCRγ δ+ IELs numbers do rise in RCD II patients after effective treatment.

The negative relationship between TCRγ δ+ and abnormal IELs, together with their known role in regulating uncomplicated celiac disease, suggests that TCRγ δ+ 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

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