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

Shomron Ben-Horin*, Sylvie Polak-Charcon, Iris Barshack, Orit Picard, Ella Fudim, Miri Yavzori, Camila Avivi, Corine Mardoukh, Avichai Shimoni, Yehuda Chowers, Yaakov Maor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)1395-1402
Number of pages8
JournalJournal of Clinical Immunology
Volume33
Issue number8
DOIs
StatePublished - Nov 2013

Funding

FundersFunder number
Sheba Medical Center

    Keywords

    • Celiac disease
    • T-cell memory response
    • bone marrow transplantation
    • gliadin
    • gluten-specific CD4+ T-cells

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