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J Exp Med ; 216(9): 2057-2070, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31270247

RESUMO

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.


Assuntos
Padrões de Herança/genética , Vacina contra Sarampo/efeitos adversos , Receptor de Interferon alfa e beta/deficiência , Vacina contra Febre Amarela/efeitos adversos , Adolescente , Alelos , Criança , Feminino , Humanos , Imunidade , Lactente , Interferon Tipo I/metabolismo , Masculino , Vacina contra Sarampo/imunologia , Proteínas Mutantes/metabolismo , Mutação/genética , Linhagem , Receptor de Interferon alfa e beta/genética , Transdução de Sinais , Vacina contra Febre Amarela/imunologia
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