Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Curr Opin Allergy Clin Immunol. 2020 Dec;20(6):574-581. doi: 10.1097/ACI.0000000000000694.
The aim of this article is to summarize recent data on rubella virus (RuV) vaccine in chronic inflammation focusing on granulomas in individuals with primary immunodeficiencies (PIDs).
The live attenuated RuV vaccine has been recently associated with cutaneous and visceral granulomas in children with various PIDs. RuV vaccine strain can persist for decades subclinically in currently unknown body site(s) before emerging in granulomas. Histologically, RuV is predominately localized in M2 macrophages in the granuloma centers. Multiple mutations accumulate during persistence resulting in emergence of immunodeficiency-related vaccine-derived rubella viruses (iVDRVs) with altered immunological, replication, and persistence properties. Viral RNA was detected in granuloma biopsies and nasopharyngeal secretions and infectious virus were isolated from the granuloma lesions. The risk of iVDRV transmissibility to contacts needs to be evaluated. Several broad-spectrum antiviral drugs have been tested recently but did not provide significant clinical improvement. Hematopoietic stem cell transplantation remains the only reliable option for curing chronic RuV-associated granulomas in PIDs.
Persistence of vaccine-derived RuVs appears to be a crucial factor in a significant proportion of granulomatous disease in PIDs. RuV testing of granulomas in PID individuals might help with case management.
本文旨在总结最近关于风疹病毒（RuV）疫苗在慢性炎症中作用的研究数据，重点关注原发性免疫缺陷（PID）患者中的肉芽肿。
最近，活减毒 RuV 疫苗与患有各种 PID 的儿童的皮肤和内脏肉芽肿有关。RuV 疫苗株可在目前未知的身体部位（多个）亚临床潜伏数十年，然后在肉芽肿中出现。组织学上，RuV 主要定位于肉芽肿中心的 M2 巨噬细胞中。在潜伏过程中会累积多个突变，从而产生具有改变的免疫、复制和持续存在特性的免疫缺陷相关疫苗衍生风疹病毒（iVDRV）。在肉芽肿活检和鼻咽分泌物中检测到病毒 RNA，并从肉芽肿病变中分离出感染性病毒。需要评估 iVDRV 对接触者的传染性风险。最近已经测试了几种广谱抗病毒药物，但没有提供显著的临床改善。造血干细胞移植仍然是治疗 PID 中慢性 RuV 相关肉芽肿的唯一可靠选择。
疫苗衍生的 RuV 的持续存在似乎是 PID 中很大一部分肉芽肿疾病的关键因素。对 PID 个体的肉芽肿进行 RuV 检测可能有助于病例管理。
