title: Celiac disease resolution after allogeneic bone marrow transplantation is associated with absence of gliadin-specific memory response by donor-derived intestinal T-cells.
abstract: OBJECTIVE
  To elucidate the relative role of the immune system and intestinal epithelium in the ethiopatogenesis of Celiac disease (CD).
  
  
  METHODS
  A patient with childhood CD who underwent allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia was followed for 5 years after resumption of gluten containing diet. Immunological memory to gliadin epitopes was assessed in the index patient and in 5 newly diagnosed CD patients by standard serology testing and by CFSE-based proliferation assays of peripheral blood CD4+ cells and of intestinal LPL towards gliadin-TTG antigens. Intestinal lymphocytes' origin was determined by combined immuno-histochemistry and fluorescent in-situ hybridiazation (FISH).
  
  
  RESULTS
  Over 5 years of follow-up after receiving BMT from a HLA-matched woman and cessation of gluten-free diet, the patient has remained well, with negative periodic antibodies assays and unremarkable serial duodenal biopsies. In vitro proliferation assays 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 evident in the newly diagnosed CD patients. Immuno-FISH of post-BMT duodenal mucosa showed that the chromosomal phenotype of all the epithelial cells was 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.
  
  
  CONCLUSIONS
  CD resolution following allogeneic BMT is associated with absent gliadin-specific memory response, and with a dichotomous lymphocyte-epithelial chimeric intestine. These observations suggest that the pathogenesis of CD is critically dependent upon the immune system rather than the epithelial compartment.
authors.affiliation: Department of Gastroenterology, Chaim Sheba Medical Center, Tel-Aviv University, Tel Hashomer, 52621, Tel-Aviv, Israel, shomron.benhorin@gmail.com.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Polak-Charcon
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Orit
authors.initials: O
authors.lastname: Picard
authors.forename: Ella
authors.initials: E
authors.lastname: Fudim
authors.forename: Miri
authors.initials: M
authors.lastname: Yavzori
authors.forename: Camila
authors.initials: C
authors.lastname: Avivi
authors.forename: Corine
authors.initials: C
authors.lastname: Mardoukh
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Maor
mesh_terms: D000328:Adult; D064591:Allografts; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D002469:Cell Separation; D005260:Female; D005500:Follow-Up Studies; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008297:Male; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D005903:Gliadin