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.
Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines
N. Hernandez, G. Bucciol, L. Moens, J. Le Pen, and M. Shahrooei contributed equally to this paper.
E. Goudouris, A. Shirkani, M. Changi-Ashtiani, and H. Rokni-Zadeh contributed equally to this paper.
S.J. Seligman, L. Abel, P. Hertzog, and N. Marr contributed equally to this paper.
****R.M. Martins, I. Meyts, Q. Zhang, M.R. MacDonald, C.M. Rice, J.-L. Casanova, E. Jouanguy, and X. Bossuyt contributed equally to this paper.
- Views Icon Views
- Share Icon Share
- Tools Icon Tools
- Search Site
Nicholas Hernandez, Giorgia Bucciol, Leen Moens, Jérémie Le Pen, Mohammad Shahrooei, Ekaterini Goudouris, Afshin Shirkani, Majid Changi-Ashtiani, Hassan Rokni-Zadeh, Esra Hazar Sayar, Ismail Reisli, Alain Lefevre-Utile, Dick Zijlmans, Andrea Jurado, Ruben Pholien, Scott Drutman, Serkan Belkaya, Aurelie Cobat, Robbert Boudewijns, Dirk Jochmans, Johan Neyts, Yoann Seeleuthner, Lazaro Lorenzo-Diaz, Chibuzo Enemchukwu, Ian Tietjen, Hans-Heinrich Hoffmann, Mana Momenilandi, Laura Pöyhönen, Marilda M. Siqueira, Sheila M. Barbosa de Lima, Denise C. de Souza Matos, Akira Homma, Maria de Lourdes S. Maia, Tamiris Azamor da Costa Barros, Patricia Mouta Nunes de Oliveira, Emersom Ciclini Mesquita, Rik Gijsbers, Shen-Ying Zhang, Stephen J. Seligman, Laurent Abel, Paul Hertzog, Nico Marr, Reinaldo de Menezes Martins, Isabelle Meyts, Qian Zhang, Margaret R. MacDonald, Charles M. Rice, Jean-Laurent Casanova, Emmanuelle Jouanguy, Xavier Bossuyt; Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines. J Exp Med 2 September 2019; 216 (9): 2057–2070. doi: https://doi.org/10.1084/jem.20182295
Download citation file: