Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients
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DOI:
10.1016/s1386-6532(99)00079-7
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发表时间:
2000-05-01
影响因子:
8.8
通讯作者:
Whitman, JE
Whitman, JE
中科院分区:
医学3区
文献类型:
--
作者:
Ablashi, DV;Eastman, HB;Whitman, JE

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背景:HHV-6是一种普遍存在的病毒,其感染多发生在儿童期,之后转为潜伏感染。HHV-6的再活化已被证明在AIDS和其他几种疾病的发病机制中起作用。目的:目的探讨HHV-6感染或再激活在多发性硬化(MS)和慢性疲劳综合征(CFS)发病机制中的作用。结果:21例MS和35例CFS患者进行了研究和临床随访。在这些患者中,我们测量了HHV-6 IgG和IgM抗体水平,并使用短期培养试验分析了其外周血单个核细胞(PBMC)中HHV-6的存在。在MS和CFS患者中,我们发现与健康对照组相比,HHV-6 IgM抗体水平较高,IgG抗体水平升高。70%的MS患者含有HHV-6晚期抗原(衣壳)的IgM抗体,而只有15%的健康供体(HD)和20%的其他神经系统疾病(OND)患者有HHV-6 IgM抗体。CFS患者IgM抗体检出率(57.1%)也高于HD患者(16%)。此外,54%的CFS患者表现出HHV-6早期蛋白(p41/38)抗体,而HD仅为8.0%。在MS和CFS患者中均检测到IgG抗体滴度升高。在短期培养试验中分析MS、CFS和HD的PBMC,以检测HHV-6抗原表达细胞,并将获得的病毒分离株表征为变体A或B。54%的MS患者含有HHV-6早期和晚期抗原产生细胞,87%的HHV-6分离株为变异体B。CFS患者的分离株主要为变异体A(70%),HD患者的分离株主要为变异体B(67%)。此外,来自OND的一个分离株也是变体B。在两名CFS患者中发现持续感染HHV-6超过2.5年,并在10名CFS患者的PBMC中检测到HHV-6特异性细胞免疫应答。结论:在MS和CFS患者中,我们发现HHV-6抗体和HHV-6 DNA水平升高。在CFS患者中也检测到细胞免疫应答的降低。这些数据表明,HHV-6再活化在这些疾病的发病机制中起作用。(C)2000 Elsevier Science B. V.保留所有权利。
Background: HHV-6 is a ubiquitous virus and its infection usually occurs in childhood and then becomes a latent infection. HHV-6 reactivation has been shown to play a role in the pathogenesis of AIDS and several other diseases. Objectives: To determine what role HHV-6 infection or reactivation plays in the pathogenesis of multiple sclerosis (MS) and chronic fatigue syndrome (CFS). Results: Twenty-one MS and 35 CFS patients were studied and followed clinically. In these patients, we measured HHV-6 IgG and IgM antibody levels and also analyzed their peripheral blood mononuclear cells (PBMCs) for the presence of HHV-6, using a short term culture assay. In both MS and CFS patients, we found higher levels of HHV-6 IgM antibody and elevated levels of IgG antibody when compared to healthy controls. Seventy percent of the MS patients studied contained IgM antibodies for HHV-6 late antigens (capsid), while only 15% of the healthy donors (HD) and 20% of the patients with other neurological disorders (OND) had HHV-6 IgM antibodies. Higher frequency of IgM antibody was also detected in CFS patients (57.1%) compared to HD (16%). Moreover, 54% of CFS patients exhibited antibody to HHV-6 early protein (p41/38) compared to only 8.0% of the HD. Elevated IgG antibody titers were detected in both the MS and the CFS patients. PBMCs from MS, CFS and HD were analyzed in a short term culture assay in order to detect HHV-6 antigen expressing cells and to characterize the viral isolates obtained as either Variant A or B. Fifty-four percent of MS patients contained HHV-6 early and late antigen producing cells and 87% of HHV-6 isolates were Variant B. Isolates from CFS, patients were predominately Variant A (70%) and isolates from HD were predominately Variant B (67%). Moreover, one isolate from OND was also Variant B. Persistent HHV-6 infection was found in two CFS patients over a period of 2.5 years and HHV-6 specific cellular immune responses were detected in PBMCs from ten CFS patients. Conclusions: In both MS and CFS patients, we found increased levels of HHV-6 antibody and HHV-6 DNA. A decrease in cellular immune responses was also detected in CFS patients. These data suggest that HHV-6 reactivation plays a role in the pathogenesis of these disorders. (C) 2000 Elsevier Science B.V. All rights reserved.