TY - JOUR
T1 - Hematopoietic Cell Transplantation Rescues Inflammatory Bowel Disease and Dysbiosis of Gut Microbiota in XIAP Deficiency
AU - Ono, Shintaro
AU - Takeshita, Kozue
AU - Kiridoshi, Yuko
AU - Kato, Motohiro
AU - Kamiya, Takahiro
AU - Hoshino, Akihiro
AU - Yanagimachi, Masakatsu
AU - Arai, Katsuhiro
AU - Takeuchi, Ichiro
AU - Toita, Nariaki
AU - Imamura, Toshihiko
AU - Sasahara, Yoji
AU - Sugita, Junichi
AU - Hamamoto, Kazuko
AU - Takeuchi, Masanobu
AU - Saito, Shoji
AU - Onuma, Masaei
AU - Tsujimoto, Hiroshi
AU - Yasui, Masahiro
AU - Taga, Takashi
AU - Arakawa, Yuki
AU - Mitani, Yuichi
AU - Yamamoto, Nobuyuki
AU - Imai, Kohsuke
AU - Suda, Wataru
AU - Hattori, Masahira
AU - Ohara, Osamu
AU - Morio, Tomohiro
AU - Honda, Kenya
AU - Kanegane, Hirokazu
N1 - Funding Information:
This work was supported by The Ministry of Education, Culture, Sports, Science of Technology/Japan Society for the Promotion of Science KAKENHI (grant no. JP17K10099) and Naoki Tsuchida Research Grant to H.K., Japan Agency for Medical Research and Development Leading Advanced Projects for Medical Innovation (grant no. JP20gm0010003) and Grant-in-Aid for Specially Promoted Research from JSPS (grant no. 20H05627 ) to K.H., and the Ministry of Health, Labour and Welfare (grant no. NCCHD 2019A-3 to K.A.).
Publisher Copyright:
© 2021 American Academy of Allergy, Asthma & Immunology
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Dysbiosis of the gut microbiota
KW - Hematopoietic cell transplantation
KW - Hemophagocytic lymphohistiocytosis
KW - Inflammatory bowel disease
KW - Microbiome
KW - Posttransplantation cyclophosphamide
KW - Reduced-intensity conditioning
KW - X-linked lymphoproliferative syndrome
KW - XIAP deficiency
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U2 - 10.1016/j.jaip.2021.05.045
DO - 10.1016/j.jaip.2021.05.045
M3 - Article
C2 - 34246792
AN - SCOPUS:85111002574
SN - 2213-2198
VL - 9
SP - 3767
EP - 3780
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 10
ER -