增强FcγRIIIA结合的登革热IgG抗体决定了疾病的严重程度
Taia T Wang1,2, Jaturong Sewatanon3,4,5, Matthew J Memoli6
1Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Science (New York, N.Y.)
|January 28, 2017
概括
反应性,非中和性免疫球蛋白G (IgG) 增加了登革热出血热 (DHF) 的风险. 甲基化IgG1抗体增强FcγRIIIA结合,导致血小板缺血和DHF/ DSS,这表明它们是治疗点.
科学领域:
- 免疫学
- 病毒学
- 传染病的发生
背景情况:
- 非中和抗体对登革热病毒感染的抗体依赖增强 (ADE) 是严重登革热的已知危险因素.
- 然而,单独存在非中和IgG并不完全解释严重登革热出血热 (DHF) 或登革热休克综合征 (DSS) 的进展.
研究的目的:
- 调查导致DENV疾病严重性的特定抗体特征.
- 确定除了简单的非中和之外的机制,这些机制将已存在的抗体与严重的登革热结局联系起来.
主要方法:
- 在DHF/ DSS患者中分析IgG Fc糖结构和分类分布.
- 使用工程抗体进行体内研究,以评估afucosylated IgG1对血小板减少的影响.
- 特定IgG概况与临床结果的相关性,包括血小板减少.
主要成果:
- DHF/ DSS患者产生的IgG对FcγRIIIA有增强的亲和力,其特征是Fc glycans和IgG1亚类的afucosylated.
- 在患有严重登革热的患者中,Afucosylated IgG1抗体被发现是丰富的.
- 这些afucosylated IgG1抗体在体内引发了血小板减少,并与血小板减少有关.
结论:
- 在DENV感染期间产生的富含IgG1的非中和IgG是导致ADE和严重疾病的关键因素.
- 针对这些特定抗体变体的产生可能是预防ADE和严重登革热的治疗策略.
- 未来的疫苗和治疗方法应旨在限制afucosylated IgG1的产生,以减轻DENV疾病的严重程度.
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