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

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.