Journal
JOURNAL OF IMMUNOLOGY
Volume 207, Issue 1, Pages 133-152Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2001451
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Funding
- National Institute of Allergy and Infectious Diseases [R37AI095983]
- National Center for Research Resources, National Center for Advancing Sciences of the National Institutes of Health [8UL1TR000043]
- Rockefeller University
- St. Giles Foundation
- INSERM
- University of Paris, Laboratoire d'Excellence Integrative-Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]
- Agence Nationale de la Recherche under Investments for the Future Grant [ANR-10-IAHU-01]
- GENMSMD [ANR-16-CE17.0005-01]
- French Ministry of Health and Clermont-Ferrand University Annee Recherche program
- National Council of Science and Technology (CONACYT) national Ph.D. fellowship
- LABEIX-IBEID
- Imagine Institute M.D
- Bettencourt-Schueller Foundation
- Imagine Institute international Ph.D. program
- Japan Society for the Promotion of Science [19H03620, 16H05355, 18KK0228]
- Practical Research Project for Rare/Intractable Diseases of the Japan Agency for Medical Research and Development
- German Federal Ministry of Education and Research (BMBF) [01GM1910C]
- Grants-in-Aid for Scientific Research [19H03620, 18KK0228] Funding Source: KAKEN
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Autosomal recessive STAT1 deficiency is a severe genetic immune disorder that predisposes patients to viral and mycobacterial infections. Patients often suffer from mycobacterial diseases and severe viral episodes, with a higher mortality rate in those with complete STAT1 deficiency. Differentiation between complete and partial forms of AR STAT1 deficiency is crucial for clinical management and outcome.
Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guerin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Herpesviridae viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.
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