Primary and Acquired Immunodeficiencies Associated With Severe Varicella-Zoster Virus Infections
Primary and Acquired Immunodeficiencies Associated With Severe Varicella-Zoster Virus Infections
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DOI：
10.1093/cid/ciaa1274
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发表时间：
2021-11-01
影响因子：
11.8
通讯作者：
Cohen, Jeffrey, I
中科院分区：
文献类型：
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作者：
Ansari, Rahila;Rosen, Lindsey B.;Cohen, Jeffrey, I
背景。虽然大多数水痘或带状疱疹病例是自限性的，但某些免疫缺陷的患者可能会发展成严重或危及生命的疾病。我们研究了一位患有水痘-带状疱疹病毒（VZV）中枢神经系统（CNS）血管病变的患者，作为评估的一部分，检测了他的血浆中细胞因子抗体。我们回顾了与原发性和获得性免疫缺陷相关的水痘或带状疱疹病例的文献。我们发现，VZV中枢神经系统血管病变患者有抗体，可中和干扰素(IFN)- α，但不能中和干扰素- γ。患者血浆在健康对照外周血单个核细胞IFN-a刺激下阻断磷酸化。除了获得性免疫缺陷，如人类免疫缺陷病毒（HIV）或IFN自身抗体外，特定基因的变异与严重水痘和/或带状疱疹有关。尽管这些基因编码的蛋白质具有非常不同的活性，但许多都影响IFN信号通路，要么是那些感知触发IFN产生的双链RNA或细胞质DNA的基因，要么是那些参与激活IFN受刺激基因以响应IFN与其受体的结合的基因。免疫缺陷突出了干扰素在控制VZV感染中的关键作用，并为某些免疫缺陷患者治疗VZV感染提出了新的方法。
Background. Although most cases of varicella or zoster are self-limited, patients with certain immune deficiencies may develop severe or life-threatening disease.Methods. We studied a patient with varicella-zoster virus (VZV) central nervous system (CNS) vasculopathy and as part of the evaluation, tested his plasma for antibodies to cytokines. We reviewed the literature for cases of varicella or zoster associated with primary and acquired immunodeficiencies.Results. We found that a patient with VZV CNS vasculopathy had antibody that neutralized interferon (IFN)-alpha but not IFN-gamma. The patient's plasma blocked phosphorylation in response to stimulation with IFN-a in healthy control peripheral blood mononuclear cells. In addition to acquired immunodeficiencies like human immunodeficiency virus (HIV) or autoantibodies to IFN, variants in specific genes have been associated with severe varicella and/or zoster. Although these genes encode proteins with very different activities, many affect IFN signaling pathways, either those that sense double-stranded RNA or cytoplasmic DNA that trigger IFN production, or those involved in activation of IFN stimulated genes in response to binding of IFN with its receptor.Conclusions. Immune deficiencies highlight the critical role of IFN in control of VZV infections and suggest new approaches for treatment of VZV infection in patients with certain immune deficiencies.