A mutation in the progesterone receptor predisposes to HEV infection in HIV-positive patients
A mutation in the progesterone receptor predisposes to HEV infection in HIV-positive patients
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DOI：
10.1111/liv.13678
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发表时间：
2018-05-01
影响因子：
6.7
通讯作者：
Boonstra, Andre
中科院分区：
文献类型：
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作者：
Debes, Jose D.;Pas, Suzan D.;Boonstra, Andre
背景和目的：戊型肝炎病毒（HEV）感染可引起免疫功能低下宿主的慢性肝病。在移植受者中，某些免疫抑制剂的使用和饮食习惯被认为是HEV的危险因素。在感染人类免疫缺陷病毒（HIV）的个体中，HEV感染的危险因素尚不清楚。我们旨在研究hiv阳性个体中名为PROGINS的孕激素受体（PR）突变与HEV感染之间的关系。方法：采用KASP方法对64例HIV阳性者和187例健康对照者的血清样本进行SNP PROGINS的检测。我们通过ELISA检测血清中IL-10和IL-12的水平，以及外周血T细胞刺激试验来检测PROGINS患者的免疫反应。结果：我们发现HIV感染者中PROGINS突变的存在与HEV血清患病率之间存在显著关联（HIV+/HEV+为30%，HIV+/HEV为2%，P = 0.009）。此外，我们发现表达PROGINS突变的HIV+/HEV+个体血清IL-10水平较低，IL-12水平较高。与没有突变的细胞相比，突变的存在导致对CD4+和CD8+ T细胞刺激的反应降低，这表明与PROGINS相关的免疫调节。结论：我们的研究确定了PR中的一个突变，为免疫抑制个体的HEV感染机制提供了重要的见解。
Background and Aims: Infection with Hepatitis E virus (HEV) can cause chronic liver disease in immunocompromised hosts. In transplant recipients, the use of certain immunosuppressants and food habits has been proposed as risk factors for HEV. In individuals infected with the human immunodeficiency virus (HIV), risk factors for HEV infection are less clear. We aimed to study the association between a mutation in the progesterone receptor (PR) named PROGINS and HEV infected in HIV-positive individuals.Methods: We evaluated the presence of the SNP PROGINS via KASP in serum samples of 64 HIV positive individuals and 187 healthy controls. We performed ELISA tests to address the serum levels of IL-10 and IL-12, as well as T cell stimulation assays in peripheral blood to address immune response in individuals with PROGINS.Results: We found a significant association between the presence of PROGINS mutation and HEV seroprevalence in individuals infected with HIV (30% in HIV+/HEV+versus 2% in HIV+/HEV, respectively, P = .009). Moreover, we found that HIV+/HEV+ individuals expressing the PROGINS mutation had lower serum levels of IL-10 and higher levels of IL-12. The presence of the mutation led to a reduced response upon stimulation of CD4+ and CD8+ T cells compared to those without the mutation, suggesting an immune modulation associated with PROGINS.Conclusions: Our study identified a mutation in the PR that provides significant insights into mechanisms of HEV infection in immunosuppressed individuals.