Higher risk of cytomegalovirus reactivation in human immunodeficiency virus-1-infected patients homozygous for MICA5.1

Higher risk of cytomegalovirus reactivation in human immunodeficiency virus-1-infected patients homozygous for MICA5.1
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DOI:
10.1016/j.humimm.2009.01.005
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发表时间:
2009-03-01
期刊:
影响因子:
2.7
通讯作者:
Witte, Torsten
Witte, Torsten
中科院分区:
医学4区
文献类型:
--
作者:
Moenkemeyer, Maren;Heiken, Hans;Witte, Torsten

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巨细胞病毒 (CMV) 感染会诱导主要组织相容性复合体 (MIC)-1 类链相关 A (MICA)(NKG2D 的配体)的表面表达。这导致自然杀伤 (NK) 和 CD8(+) T 细胞更好地识别和消除感染细胞。 MICA5.1 等位基因编码截短的蛋白质。本研究旨在测试功能性 MICA 蛋白表达受损是否会影响免疫功能低下个体对严重 CMV 再激活的易感性。在这项研究中,通过聚合酶链反应评估了 230 名高加索人类免疫缺陷病毒 (HIV)-1 感染患者和 219 名健康对照者中 MICA5.1 的频率。合并感染丙型肝炎病毒(HCV)和 GB 病毒 C 的患者作为对照。通过聚合酶链式反应分析MICA5.1等位基因。通过 Pearson chi(2) 检验计算 MICA5.1 纯合性与 CMV 再激活风险的关联。对有和没有 CMV 疾病表现史的患者进行比较显示,CMV 再激活患者中纯合 MICA5.1 基因型的出现频率 (33%) 明显高于无 CMV 激活患者的频率 (16%;p = 0.032;比值比 = 0.330)。 HIV-1 感染者和健康对照者的比例相似。此外,HCV和GB病毒-C感染的MICA5.1频率没有差异。我们的研究首次在体内证明了免疫功能低下个体中纯合 MICA5.1 基因型与 CMV 再激活易感性之间的关联。 (C) 2009 学会。由爱思唯尔公司出版。保留所有权利。
infection with cytomegalovirus (CMV) induces surface expression of major histocompatibility complex (MIC)-class-1-chain-related A (MICA), a ligand for NKG2D. This leads to improved recognition and elimination of infected cells by natural killer (NK) as well as CD8(+) T cells. The MICA5.1 allele codes for a truncated protein. This study was performed to test whether impaired expression of a functional MICA protein would influence the susceptibility to severe CMV reactivation in immunocompromised individuals. In this study, the frequency of MICA5.1 was assessed by polymerase chain reaction in 230 Caucasian human immunodeficiency virus (HIV)-1-infected patients and in 219 healthy controls. Patients co-infected with hepatitis C Virus (HCV) and GB virus-C served as controls. MICA5.1 allele was analyzed by polymerase chain reaction. Association of MICA5.1 homozygosity and risk of CMV reactivation was calculated by Pearson chi(2) test. Comparison of patients with and without a history of CMV disease manifestation revealed that homozygous MICA5.1 genotype was present in a significantly higher frequency in patients with CMV reactivation (33%) than in those without (16%; p = 0.032; odds ratio = 0.330). The percentage was similar in HIV-1-infected patients and healthy controls. Furthermore, there was no difference in the frequency of MICA5.1 with respect to infection with HCV and GB virus-C. Our study provides the first in vivo demonstration of an association between homozygous MICA5.1 genotype and susceptibility to CMV reactivation in immunocompromised individuals. (C) 2009 Society. Published by Elsevier Inc. All rights reserved.