St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.
Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
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 , , or ). 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 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 Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.
接种麻疹、腮腺炎和风疹（MMR）和黄热病（YF）减毒活疫苗很少会导致危及生命的疾病。I 型和/或 III 型干扰素（IFN）免疫（ 、 或 基因突变）先天缺陷可导致严重的 MMR 疫苗疾病。YF 疫苗的不良反应仍未得到解释。我们报告了两名健康状况良好的患者，一名伊朗 9 岁男孩在 1 岁时出现严重麻疹疫苗疾病，一名巴西 14 岁女孩在 12 岁时因 YF 疫苗引起内脏疾病。伊朗患者为纯合子，巴西患者为功能丧失 变异的复合杂合子。在缺乏或存在外源性 I 型 IFN 的情况下，患者来源的成纤维细胞易受病毒（包括 YF 和麻疹病毒疫苗株）的影响。用 WT 可挽救患者成纤维细胞表型。常染色体隐性遗传、完全 IFNAR1 缺乏症可导致先前健康个体接种减毒麻疹和风疹病毒活疫苗的严重并发症。
