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


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.

SUBMITTER: Hernandez N 

PROVIDER: S-EPMC6719432 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Hernandez Nicholas N   Bucciol Giorgia G   Moens Leen L   Le Pen Jérémie J   Shahrooei Mohammad M   Goudouris Ekaterini E   Shirkani Afshin A   Changi-Ashtiani Majid M   Rokni-Zadeh Hassan H   Sayar Esra Hazar EH   Reisli Ismail I   Lefevre-Utile Alain A   Zijlmans Dick D   Jurado Andrea A   Pholien Ruben R   Drutman Scott S   Belkaya Serkan S   Cobat Aurelie A   Boudewijns Robbert R   Jochmans Dirk D   Neyts Johan J   Seeleuthner Yoann Y   Lorenzo-Diaz Lazaro L   Enemchukwu Chibuzo C   Tietjen Ian I   Hoffmann Hans-Heinrich HH   Momenilandi Mana M   Pöyhönen Laura L   Siqueira Marilda M MM   de Lima Sheila M Barbosa SMB   de Souza Matos Denise C DC   Homma Akira A   Maia Maria de Lourdes S MLS   da Costa Barros Tamiris Azamor TA   de Oliveira Patricia Mouta Nunes PMN   Mesquita Emersom Ciclini EC   Gijsbers Rik R   Zhang Shen-Ying SY   Seligman Stephen J SJ   Abel Laurent L   Hertzog Paul P   Marr Nico N   Martins Reinaldo de Menezes RM   Meyts Isabelle I   Zhang Qian Q   MacDonald Margaret R MR   Rice Charles M CM   Casanova Jean-Laurent JL   Jouanguy Emmanuelle E   Bossuyt Xavier X  

The Journal of experimental medicine 20190703 9


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 <i>IFNAR2</i>, <i>STAT1</i>, or <i>STAT2</i>). 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-y  ...[more]

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