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Celiac disease resolution after allogeneic bone marrow transplantation is associated with absence of gliadin-specific memory response by donor-derived intestinal T-cells.

Abstract：

PURPOSE: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.

journal_name

J Clin Immunol

journal_title

Journal of clinical immunology

authors

Ben-Horin S,Polak-Charcon S,Barshack I,Picard O,Fudim E,Yavzori M,Avivi C,Mardoukh C,Shimoni A,Chowers Y,Maor Y

doi

10.1007/s10875-013-9943-9

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

1395-402

issue

eissn

0271-9142

issn

1573-2592

journal_volume

pub_type

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Celiac disease resolution after allogeneic bone marrow transplantation is associated with absence of gliadin-specific memory response by donor-derived intestinal T-cells.