IF 12.6 1区 医学 Q1 IMMUNOLOGY
Journal of Experimental Medicine Pub Date : 2025-02-03 Epub Date: 2024-12-16 DOI:10.1084/jem.20241413
Fahd Al Qureshah, Jérémie Le Pen, Nicole A de Weerd, Marcela Moncada-Velez, Marie Materna, Daniel C Lin, Baptiste Milisavljevic, Fernanda Vianna, Lucy Bizien, Lazaro Lorenzo, Marc Lecuit, Jean-David Pommier, Sevgi Keles, Tayfun Ozcelik, Sigifredo Pedraza-Sanchez, Nicolas de Prost, Loubna El Zein, Hassan Hammoud, Lisa F P Ng, Rabih Halwani, Narjes Saheb Sharif-Askari, Yu Lung Lau, Anthony R Tam, Neha Singh, Sagar Bhattad, Yackov Berkun, Wasun Chantratita, Raúl Aguilar-López, Mohammad Shahrooei, Laurent Abel, Paul Bastard, Emmanuelle Jouanguy, Vivien Béziat, Peng Zhang, Charles M Rice, Aurélie Cobat, Shen-Ying Zhang, Paul J Hertzog, Jean-Laurent Casanova, Qian Zhang
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引用次数: 0

摘要

人类 I 型 IFN 受体 IFNAR1 或 IFNAR2 链的常染色体隐性缺乏症会导致细胞对 IFN-α、-β 和 -ω 的反应消失,是严重病毒性疾病的基础,而且在全球范围内非常罕见,只有西波利尼西亚和北极地区分别存在 IFNAR1 和 IFNAR2 缺乏症。我们报告了 11 个人类 IFNAR1 等位基因,这些等位基因的产物会损害但不会消除对 IFN-α 和 -ω 的反应,而不会影响对 IFN-β 的反应。这些等位基因中有 10 个在所有研究人群中都很罕见,但剩下的一个等位基因(P335del)在中国南方很常见(小等位基因频率≈2%)。杂合这些变异体的细胞在体外显示出显性表型,对 IFN-α 和 -ω 的反应减弱,但对 -β 的反应不减弱,对病毒的敏感性也减弱。造成这种显性的原因是负显性,而不是单倍性缺失。这些变异体的杂合子患者易患病毒性疾病,这既证明了这些变异体在临床上的优势,也证明了 IFN-α 和 -ω 对某些病毒的保护性免疫的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%). Cells heterozygous for these variants display a dominant phenotype in vitro with impaired responses to IFN-α and -ω, but not -β, and viral susceptibility. Negative dominance, rather than haploinsufficiency, accounts for this dominance. Patients heterozygous for these variants are prone to viral diseases, attesting to both the dominance of these variants clinically and the importance of IFN-α and -ω for protective immunity against some viruses.

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来源期刊
CiteScore
26.60
自引率
1.30%
发文量
189
审稿时长
3-8 weeks
期刊介绍: Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.
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