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Gut immune reconstitution in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome after hematopoietic stem cell transplantation  Eleonora.

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Presentation on theme: "Gut immune reconstitution in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome after hematopoietic stem cell transplantation  Eleonora."— Presentation transcript:

1 Gut immune reconstitution in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome after hematopoietic stem cell transplantation  Eleonora Gambineri, MD, Sara Ciullini Mannurita, MSc, Helen Robertson, PhD, Marina Vignoli, PhD, Beate Haugk, MD, Paolo Lionetti, MD, PhD, Sophie Hambleton, MD, PhD, Dawn Barge, PhD, Andrew R. Gennery, MD, Mary Slatter, MD, Zohreh Nademi, MD, Terence J. Flood, MD, Anthony Jackson, PhD, Mario Abinun, MD, Andrew J. Cant, MD  Journal of Allergy and Clinical Immunology  Volume 135, Issue 1, Pages e8 (January 2015) DOI: /j.jaci Copyright © 2014 The Authors Terms and Conditions

2 Fig 1 FOXP3 “reactive nuclei” (arrow) in and around lymphoid follicles in small bowel mucosa and submucosa on immunohistochemically stained sections at 3 months (A), 6 months (B), and 9 months (C) post-transplant. (FOXP3 reactive nuclei are stained black, and the sections are counterstained with hematoxylin.) D, Quantitative analysis of FOXP3+nuclei in the examined total small bowel mucosal and submucosal tissue. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

3 Fig 2 Exon 9 FOXP3 sequencing and chimerism analysis on laser microdissected CD4+ T cells from small bowel biopsies at 3 months post-transplant (A) and on CD31−CD4+α4β7high memory T cells (B) and CD31+CD4+α4β7low naive T cells (C) sorted from peripheral blood at 9 months post-transplant. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

4 Fig E1 Immunohistochemical staining for FOXP3+ cells in pretransplant small bowel mucosa and submucosa section from small bowel biopsy (FOXP3 reactive nuclei are stained black, and the sections are counterstained with hematoxylin). Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

5 Fig E2 Intracytoplasmic FOXP3 expression in peripheral blood cells before and at indicated time points after transplant. Gates for analysis were set on CD4+CD25+bright T cells. x axis/arrow, Fluorescence intensity; y axis, cell counts. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

6 Fig E3 Timeline representing experiments and analysis performed during this study. HE, Hematoxylin-eosin. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

7 Fig E4 Absolute count of T, B, and natural killer (NK) cells (per uL blood) in peripheral blood pre- and post-HSCT (3, 6, 9, and 12 months). Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

8 Fig E5 Donor cell chimerism in peripheral blood T cells (CD3+), B cells (CD19+), and monocytes (CD15+) during 1 year post-transplant, shown in months (m). Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

9 Fig E6 Histopathological findings of the resected small bowel specimens. Hematoxylin-eosin (HE) staining showed loss of mucosal epithelium with total villous atrophy at both 3 months (A) and 4 months (B) post-transplant and long slender villi with normal brush borders at 6 months post-transplant (C). No histologic evidence of GvHD. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © 2014 The Authors Terms and Conditions

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