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J Exp Med. 2019 Jul 3. pii: jem.20182295. doi: 10.1084/jem.20182295. [Epub ahead of print]

Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines.

Author information

1
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.
2
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
3
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY.
4
Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran.
5
Department of Microbiology and Immunology, Clinical and Diagnostic Immunology, KU Leuven, Leuven, Belgium.
6
Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
7
Allergy and Clinical Immunology Department, Bushehr University of Medical Science, School of Medicine, Bushehr, Iran.
8
School of Mathematics, Institute for Research in Fundamental Sciences, Tehran, Iran.
9
Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
10
Department of Pediatrics, Division of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.
11
Pediatrics Department, Jean Verdier Hospital, Assistance Publique des Hôpitaux de Paris, Paris 13 University, Bondy, France.
12
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
13
Pediatric Immunology-Hematology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France.
14
Paris Descartes University, Imagine Institute, Paris, France.
15
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Paris, France.
16
National Reference Laboratory for Respiratory Viruses, Institute Oswaldo Cruz, Fiocruz, Ministry of Health, Rio de Janeiro, Brazil.
17
Laboratory of Virological Techniques, Bio-Manguinhos, Fiocruz, Ministry of Health, Rio de Janeiro, Brazil.
18
Laboratory of Immunological Techniques, Bio-Manguinhos, Fiocruz, Ministry of Health, Rio de Janeiro, Brazil.
19
Bio-Manguinhos, Fiocruz, Ministry of Health, Rio de Janeiro, Brazil.
20
Laboratory for Viral Vector Technology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
21
Leuven Viral Vector Core, Leuven, Belgium.
22
Department of Microbiology and Immunology, New York Medical College, Valhalla, NY.
23
Hudson Institute of Medical Research, Clayton, Victoria, Australia.
24
Division of Translational Medicine, Sidra Medicine, Doha, Qatar.
25
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
26
Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
27
Precision Immunology Institute and Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai, New York, NY.
28
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY casanova@rockefeller.edu.
29
Howard Hughes Medical Institute, New York, NY.
30
Department of Microbiology, Immunology and Transplantation, Clinical and Diagnostic Immunology, KU Leuven, Leuven, Belgium.
31
Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
#
Contributed equally

Abstract

Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients' fibroblast phenotypes are rescued with WT IFNAR1 Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.

PMID:
31270247
DOI:
10.1084/jem.20182295

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