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Phenotype, genotype, treatment, and survival outcomes in patients with X-linked inhibitor of apoptosis deficiency

Yang, L; Booth, C; Speckmann, C; Seidel, MG; Worth, AJ; Kindle, G; Lankester, AC; ... Burns, SO; + view all (2022) Phenotype, genotype, treatment, and survival outcomes in patients with X-linked inhibitor of apoptosis deficiency. Journal of Allergy and Clinical Immunology , 150 (2) pp. 456-466. 10.1016/j.jaci.2021.10.037. Green open access

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Abstract

BACKGROUND: X-linked inhibitor of apoptosis (XIAP) deficiency is a rare, primary immunodeficiency disease caused by XIAP gene mutations. A broad range of phenotype, severity, and age of onset present challenges for patient management. OBJECTIVE: To characterize the phenotype, treatment, and survival outcomes of XIAP deficiency and assess parameters influencing prognosis. METHODS: Data published from 2006-2020 were retrospectively analyzed. RESULTS: 167 patients from 117 families with XIAP deficiency were reported with 90 different mutations. A wide spectrum of clinical features were seen, of which hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) were the most common. Patients frequently developed multiple features with no clear genotype-phenotype correlation. 117 patients were managed conservatively and 50 underwent hematopoietic stem cell transplantation (HSCT), with respective overall survival probabilities of 90% and 53% at age 16 years. The predominant indication for HSCT was early-onset HLH. Active HLH and myeloablative conditioning regimens increased HSCT-related mortality, although HSCT outcome was much better after 2015 than before. For conservatively managed patients reaching adulthood, survival probabilities were 86% at age 30 years and 37% by age 52 years, with worse outcomes for patients developing the disease before the age of 5 years or with new disease features in adulthood. 9 asymptomatic mutation carriers were identified with a median age of 13.5 years. CONCLUSIONS: Our study demonstrates the variable nature of XIAP deficiency which evolves over life for individual patients. Better therapeutic strategies and prospective studies are required to reduce morbidity and mortality and improve decision-making and long-term outcomes for patients with XIAP deficiency.

Type: Article
Title: Phenotype, genotype, treatment, and survival outcomes in patients with X-linked inhibitor of apoptosis deficiency
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jaci.2021.10.037
Publisher version: https://doi.org/10.1016/j.jaci.2021.10.037
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Primary Immunodeficiency, X-linked inhibitor of apoptosis, phenotype, survival outcomes, therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10141329
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