Hematopoietic Cell Transplantation Rescues Inflammatory Bowel Disease and Dysbiosis of Gut Microbiota in XIAP Deficiency

Shintaro Ono, Kozue Takeshita, Yuko Kiridoshi, Motohiro Kato, Takahiro Kamiya, Akihiro Hoshino, Masakatsu Yanagimachi, Katsuhiro Arai, Ichiro Takeuchi, Nariaki Toita, Toshihiko Imamura, Yoji Sasahara, Junichi Sugita, Kazuko Hamamoto, Masanobu Takeuchi, Shoji Saito, Masaei Onuma, Hiroshi Tsujimoto, Masahiro Yasui, Takashi TagaYuki Arakawa, Yuichi Mitani, Nobuyuki Yamamoto, Kohsuke Imai, Wataru Suda, Masahira Hattori, Osamu Ohara, Tomohiro Morio, Kenya Honda, Hirokazu Kanegane

Research output: Contribution to journalArticlepeer-review

Abstract

Background: X-linked inhibitor of apoptosis protein (XIAP) deficiency is an infrequent inborn error of immunity that is often associated with refractory inflammatory bowel disease (IBD). The natural course of XIAP deficiency is typically associated with poor prognosis, and hematopoietic cell transplantation (HCT) is the only curative treatment. Objective: To study (1) the effect of HCT on patients with XIAP deficiency undergoing HCT, (2) the status of XIAP deficiency–associated IBD after HCT, and (3) the gut microbiota of XIAP deficiency–associated IBD before and after HCT. Methods: A nationwide survey of patients with XIAP deficiency was conducted. A spreadsheet questionnaire was collected from the physicians. Feces samples collected from the patients before and after HCT and their healthy family members were analyzed. Results: Twenty-six patients with XIAP deficiency underwent HCT by the end of March 2020, and 22 patients (84.6%) survived. All the survivors underwent a fludarabine-based reduced-intensity condition regimen. Acute graft-versus-host disease was observed in 17 patients (65.4%). Nineteen patients experienced refractory IBD before undergoing HCT. IBD improved remarkably after HCT. After HCT, the colonoscopic and pathological symptoms were restored to normal, and the pediatric ulcerative colitis activity index improved significantly. Gut microbiota indicated dysbiosis before HCT; however, it was improved to resemble that of the healthy family members after HCT. Conclusions: This study revealed that HCT has a favorable outcome for XIAP deficiency. HCT rescues gut inflammation and dysbiosis in patients with XIAP deficiency.

Original languageEnglish
Pages (from-to)3767-3780
Number of pages14
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume9
Issue number10
DOIs
Publication statusPublished - 2021 Oct
Externally publishedYes

Keywords

  • Dysbiosis of the gut microbiota
  • Hematopoietic cell transplantation
  • Hemophagocytic lymphohistiocytosis
  • Inflammatory bowel disease
  • Microbiome
  • Posttransplantation cyclophosphamide
  • Reduced-intensity conditioning
  • X-linked lymphoproliferative syndrome
  • XIAP deficiency

ASJC Scopus subject areas

  • Immunology and Allergy

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