A CHRONIC ILLNESS CHARACTERIZED BY FATIGUE, NEUROLOGIC AND IMMUNOLOGICAL DISORDERS, AND ACTIVE HUMAN HERPESVIRUS TYPE-6 INFECTION

A CHRONIC ILLNESS CHARACTERIZED BY FATIGUE, NEUROLOGIC AND IMMUNOLOGICAL DISORDERS, AND ACTIVE HUMAN HERPESVIRUS TYPE-6 INFECTION
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DOI:
10.7326/0003-4819-116-2-103
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发表时间:
1992-01-15
影响因子:
39.2
通讯作者:
KOMAROFF, AL
KOMAROFF, AL
中科院分区:
医学1区
文献类型:
--
作者:
BUCHWALD, D;CHENEY, PR;KOMAROFF, AL

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目的:对急性发作的慢性衰弱性疾病患者进行神经学、免疫学和病毒学研究。设计:与匹配的健康对照组进行比较的队列研究。患者:我们研究了259例在一个医疗实践中寻求护理的患者; 29%的患者经常卧床不起或关在家里。主要结果测量:详细病史、体格检查、常规血液学和化学检测、磁共振成像(MRI)研究、淋巴细胞表型研究,以及用人类疱疹病毒6型(HHV-6)检测患者淋巴细胞的活动性感染。患者的平均(+/- SD)CD 4/CD 8 T细胞比率高于匹配的健康对照组(分别为3.16 +/- 1.5和2.3 +/- 1.0; P < 0.003)。脑磁共振扫描显示78%的患者(95%CI,72%至86%)和21%的对照组(CI,11%至36%)(P < 10 - 9)的高信号皮质下区域与水肿或脱髓鞘一致。淋巴细胞原代培养显示79例HHV-6复制活跃(70%; Cl,61%至78%),40例对照中有8例(20%; Cl,9%至36%)(P < 10(-8)),这一发现得到了HHV-6蛋白特异性单克隆抗体检测和HHV-6 DNA特异性聚合酶链反应检测的证实。神经系统症状、MRI结果和淋巴细胞表型研究表明,患者可能经历了慢性、免疫介导的中枢神经系统炎症过程。HHV-6的活跃复制很可能代表潜伏感染的重新激活,可能是由于免疫功能障碍。我们的研究并没有直接说明HHV-6,一种嗜淋巴细胞和胶质细胞的病毒,是否在产生这种疾病的症状或免疫和神经功能障碍中起作用。我们的患者来自一个相对较小的地理区域,我们的研究结果是否可以推广到其他患有类似综合征的患者还有待观察。
Objective: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset.Design: Cohort study with comparison to matched, healthy control subjects.Patients: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in.Main Outcome Measures: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6).Main Results: Patients had a higher mean (+/- SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 +/- 1.5 compared with 2.3 +/- 1.0, respectively; P < 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% Cl, 72% to 86%) and in 21% of controls (Cl, 11% to 36%) (P < 10(-9)). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; Cl, 61% to 78%) and in 8 of 40 controls (20%; Cl, 9% to 36%) (P < 10(-8)), a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA.Conclusions: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen.