Science translational medicine · 2015
Human IFNAR2 deficiency: Lessons for antiviral immunity.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Duncan Christopher J A, Mohamad Siti M B, Young Dan F, Skelton Andrew J, Leahy T Ronan, Munday Diane C, Butler Karina M, Morfopoulou Sofia, Brown Julianne R, Hubank Mike, Connell Jeff, Gavin Patrick J, McMahon Cathy, Dempsey Eugene, Lynch Niamh E, Jacques Thomas S, Valappil Manoj, Cant Andrew J, Breuer Judith, Engelhardt Karin R, Randall Richard E, Hambleton Sophie
Аннотация
Type I interferon (IFN-α/β) is a fundamental antiviral defense mechanism. Mouse models have been pivotal to understanding the role of IFN-α/β in immunity, although validation of these findings in humans has been limited. We investigated a previously healthy child with fatal encephalitis after inoculation of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted resequencing, we identified a homozygous mutation in the high-affinity IFN-α/β receptor (IFNAR2) in the proband, as well as a newborn sibling, that rendered cells unresponsive to IFN-α/β. Reconstitution of the proband's cells with wild-type IFNAR2 restored IFN-α/β responsiveness and control of IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine challenge, the proband had previously shown no evidence of heightened susceptibility to respiratory viral pathogens. The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-α/β in human antiviral immunity.