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INHERITED IFNAR1 DEFICIENCY IN OTHERWISE HEALTHY PATIENTS WITH ADVERSE REACTION TO MEASLES AND YELLOW FEVER LIVE VACCINES
Author
Hernandez, Nicholas
Bucciol, Giorgia
Moens, Leen
Le Pen, Jérémie
Shahrooei, Mohammad
Goudouris, Ekaterini
Shirkani, Afshin
Changi-Ashtiani, Majid
Rokni-Zadeh, Hassan
Sayar, Esra Hazar
Reisli, Ismail
Lefevre-Utile, Alain
Zijlmans, Dick
Jurado, Andrea
Pholien, Ruben
Drutman, Scott
Belkaya, Serkan
Cobat, Aurelie
Boudewijns, Robbert
Jochmans, Dirk
Neyts, Johan
Seeleuthner, Yoann
Lorenzo-Diaz, Lazaro
Enemchukwu, Chibuzo
Tietjen, Ian
Hoffmann, Hans-Heinrich
Momenilandi, Mana
Pöyhönen, Laura
Siqueira, Marilda Agudo Mendonça Teixeira de
Lima, Sheila M Barbosa de
Matos, Denise C. de Souza
Homma, Akira
Maia, Maria de Lourdes S.
Barros, Tamiris Azamor da Costa
Oliveira, Patricia Mouta Nunes de
Mesquita, Emersom Ciclini
Gijsbers, Rik
Zhang, Shen-Ying
Seligman, Stephen J.
Abel, Laurent
Hertzog, Paul
Marr, Nico
Martins, Reinaldo de Menezes
Meyts, Isabelle
Zhang, Qian
MacDonald, Margaret R.
Rice, Charles M.
Casanova, Jean-Laurent
Jouanguy, Emmanuelle
Bossuyt, Xavier
Bucciol, Giorgia
Moens, Leen
Le Pen, Jérémie
Shahrooei, Mohammad
Goudouris, Ekaterini
Shirkani, Afshin
Changi-Ashtiani, Majid
Rokni-Zadeh, Hassan
Sayar, Esra Hazar
Reisli, Ismail
Lefevre-Utile, Alain
Zijlmans, Dick
Jurado, Andrea
Pholien, Ruben
Drutman, Scott
Belkaya, Serkan
Cobat, Aurelie
Boudewijns, Robbert
Jochmans, Dirk
Neyts, Johan
Seeleuthner, Yoann
Lorenzo-Diaz, Lazaro
Enemchukwu, Chibuzo
Tietjen, Ian
Hoffmann, Hans-Heinrich
Momenilandi, Mana
Pöyhönen, Laura
Siqueira, Marilda Agudo Mendonça Teixeira de
Lima, Sheila M Barbosa de
Matos, Denise C. de Souza
Homma, Akira
Maia, Maria de Lourdes S.
Barros, Tamiris Azamor da Costa
Oliveira, Patricia Mouta Nunes de
Mesquita, Emersom Ciclini
Gijsbers, Rik
Zhang, Shen-Ying
Seligman, Stephen J.
Abel, Laurent
Hertzog, Paul
Marr, Nico
Martins, Reinaldo de Menezes
Meyts, Isabelle
Zhang, Qian
MacDonald, Margaret R.
Rice, Charles M.
Casanova, Jean-Laurent
Jouanguy, Emmanuelle
Bossuyt, Xavier
Affilliation
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex. Ahvaz, Iran / Department of Microbiology and Immunology. Clinical and Diagnostic Immunology. KU Leuven, Leuven, Belgium.
Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Allergy and Clinical Immunology Department, Bushehr University of Medical Science, School of Medicine, Bushehr, Iran.
School of Mathematics, Institute for Research in Fundamental Sciences. Tehran, Iran.
Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences. Zanjan, Iran.
Department of Pediatrics, Division of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.
Department of Pediatrics, Division of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.
Pediatrics Department, Jean Verdier Hospital, Assistance Publique des Hopitaux de Paris, Paris 13, University, Bondy, France.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Pediatric Immunology-Hematology Unit, Assistance Publique-Hopitaux de Paris, Necker Hospital for Sick Children, Paris, France.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
Paris Descartes University, Imagine Institute. Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163. Paris, France.
Paris Descartes University, Imagine Institute. Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163. Paris, France.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Ministério da Saúde. Fundação Oswaldo Cruz. Instituto Osvaldo Cruz. Laboratório Nacional de Referência em Vírus Respiratório. Rio de Janeiro, RJ, Brasil. .
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Laboratório de Técnicas Virológicas. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Laboratório de Técnicas Imunológicas. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Laboratório de Técnicas Imunológicas. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Laboratory for Viral Vector Technology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium / Leuven Viral Vector Core, Leuven, Belgium.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163, Paris, France.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium..
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163, Paris, France.
Hudson Institute of Medical Research. Clayton, Victoria, Australia.
Division of Translational Medicine, Sidra Medicine, Doha, Qatar / College of Health and Life Sciences, Hamad Bin Khalifa University. Doha, Qatar.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation. KU Leuven, Leuven, Belgium / Department of Pediatrics, University Hospitals. Leuven, Leuven, Belgium.
7Precision Immunology Institute and Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai. New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Precision Immunology Institute and Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai, New York, NY
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Laboratory of Virology and Infectious Disease. The Rockefeller University, New York, NY, USA.
Laboratory of Virology and Infectious Disease. The Rockefeller University, New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Pediatric Immunology-Hematology Unit, Assistance Publique-Hopitaux de Paris, Necker Hospital for Sick Children, Paris, France / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale ´ U1163, Paris, France / Howard Hughes Medical Institute New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche M ´ edicale ´ U1163, Paris, France.
Department of Microbiology, Immunology and Transplantation, Clinical and Diagnostic Immunology. KU Leuven, Leuven, Belgium.
Department of Laboratory Medicine, University Hospitals Leuven. Leuven, Belgium.
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex. Ahvaz, Iran / Department of Microbiology and Immunology. Clinical and Diagnostic Immunology. KU Leuven, Leuven, Belgium.
Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Allergy and Clinical Immunology Department, Bushehr University of Medical Science, School of Medicine, Bushehr, Iran.
School of Mathematics, Institute for Research in Fundamental Sciences. Tehran, Iran.
Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences. Zanjan, Iran.
Department of Pediatrics, Division of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.
Department of Pediatrics, Division of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.
Pediatrics Department, Jean Verdier Hospital, Assistance Publique des Hopitaux de Paris, Paris 13, University, Bondy, France.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Pediatric Immunology-Hematology Unit, Assistance Publique-Hopitaux de Paris, Necker Hospital for Sick Children, Paris, France.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research. KU Leuven, Leuven, Belgium.
Paris Descartes University, Imagine Institute. Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163. Paris, France.
Paris Descartes University, Imagine Institute. Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163. Paris, France.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
The Rockefeller University. Laboratory of Virology and Infectious Disease. New York, NY, USA.
Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Ministério da Saúde. Fundação Oswaldo Cruz. Instituto Osvaldo Cruz. Laboratório Nacional de Referência em Vírus Respiratório. Rio de Janeiro, RJ, Brasil. .
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Laboratório de Técnicas Virológicas. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Laboratório de Técnicas Imunológicas. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Laboratório de Técnicas Imunológicas. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Laboratory for Viral Vector Technology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium / Leuven Viral Vector Core, Leuven, Belgium.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163, Paris, France.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium..
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale U1163, Paris, France.
Hudson Institute of Medical Research. Clayton, Victoria, Australia.
Division of Translational Medicine, Sidra Medicine, Doha, Qatar / College of Health and Life Sciences, Hamad Bin Khalifa University. Doha, Qatar.
Ministério da Saúde. Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation. KU Leuven, Leuven, Belgium / Department of Pediatrics, University Hospitals. Leuven, Leuven, Belgium.
7Precision Immunology Institute and Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai. New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Precision Immunology Institute and Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai, New York, NY
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA.
Laboratory of Virology and Infectious Disease. The Rockefeller University, New York, NY, USA.
Laboratory of Virology and Infectious Disease. The Rockefeller University, New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Pediatric Immunology-Hematology Unit, Assistance Publique-Hopitaux de Paris, Necker Hospital for Sick Children, Paris, France / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Médicale ´ U1163, Paris, France / Howard Hughes Medical Institute New York, NY, USA.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University, New York, NY, USA / Paris Descartes University, Imagine Institute, Paris, France / Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche M ´ edicale ´ U1163, Paris, France.
Department of Microbiology, Immunology and Transplantation, Clinical and Diagnostic Immunology. KU Leuven, Leuven, Belgium.
Department of Laboratory Medicine, University Hospitals Leuven. Leuven, Belgium.
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.
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