Celiac.com 01/06/2014 - A team of researchers recently set out to clarify the role of the immune system and intestinal epithelium in the origins of celiac disease.

Bone Marrow Diagram: CC--Wikimedia CommonsThe research team included S. Ben-Horin, S. Polak-Charcon,I. Barshack, O. Picard, E. Fudim, M. Yavzori, C. Avivi, C. Mardoukh, A. Shimoni, Y Chowers, Y. and Maor, of the Department of Gastroenterology in Chaim Sheba Medical Center at Tel-Aviv University, Tel Hashomer in Tel-Aviv, Israel.

For five years, the team followed a patient with childhood celiac disease who had undergone an allogeneic bone marrow transplant (BMT) for chronic myelogenous leukemia, and subsequently resumed consuming a gluten-containing diet.

Using standard serology testing, along with CFSE-based proliferation assays of peripheral blood CD4+ cells and of intestinal LPL towards gliadin-TTG antigens, the team assessed immunological memory to gliadin epitopes in both the control patient and in 5 newly diagnosed celiac patients.

They used combined immuno-histochemistry and fluorescent in-situ hybridiazation (FISH) to determine the origin of the intestinal lymphocytes.

They found that the patient remained healthy for more than 5 years of follow-up after receiving BMT from a HLA-matched woman, and ceasing the gluten-free diet. The continued to show negative periodic antibodies tests and unremarkable serial duodenal biopsies.

In vitro tests showed lack of a memory response of the patient's peripheral blood and lamina propria CD4+ T-cells towards TTG, gliadin or TTG-treated gliadin, whereas memory responses were common in the newly diagnosed celiac patients.

Immuno-FISH of post-BMT duodenal mucosa showed that all the epithelial cells had the chromosomal phenotype of XY. In contrast, CD45+ lymphocytic lineage cells were all donor-derived XX cells, presumably originating in the transplanted bone marrow and re-populating the intestinal wall.

The resolution of celiac disease after allogeneic BMT does occur, and is associated with absent gliadin-specific memory response, and with a dichotomous lymphocyte-epithelial chimeric intestine. These findings suggest that the origins of celiac disease are deeply connected to the immune system, rather than the epithelial area.


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