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

J Exp Med. 2019 Sep 2;216(9):2057-2070. doi: 10.1084/jem.20182295. Epub 2019 Jul 3.


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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Child
  • Female
  • Humans
  • Immunity
  • Infant
  • Inheritance Patterns / genetics*
  • Interferon Type I / metabolism
  • Male
  • Measles Vaccine / adverse effects*
  • Measles Vaccine / immunology
  • Mutant Proteins / metabolism
  • Mutation / genetics
  • Pedigree
  • Receptor, Interferon alpha-beta / deficiency*
  • Receptor, Interferon alpha-beta / genetics
  • Signal Transduction
  • Yellow Fever Vaccine / adverse effects*
  • Yellow Fever Vaccine / immunology


  • IFNAR1 protein, human
  • Interferon Type I
  • Measles Vaccine
  • Mutant Proteins
  • Yellow Fever Vaccine
  • Receptor, Interferon alpha-beta