London School of Hygiene & Tropical Medicine, Faculty of Infectious and Tropical Diseases, London, United Kingdom.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
J Infect Dis. 2020 Mar 16;221(7):1127-1134. doi: 10.1093/infdis/jiz581.
Recent evidence highlights human cytomegalovirus (HCMV) and immune activation as risk factors for tuberculosis disease. It is not known whether other herpesviruses are also implicated, nor whether a dose-response relationship exists between tuberculosis risk and herpes coinfection.
This nested case-control study used stored serum samples from 25 persons with tuberculosis up to 10 years before tuberculosis diagnosis and between 3 and 6 matched controls without tuberculosis from a rural Ugandan cohort. Samples were investigated for Epstein-Barr virus, herpes simplex virus, and HCMV-specific immunoglobulin G (IgG), serum markers of inflammation, and mycobacterial antibody levels.
Humoral response to HCMV, but not Epstein-Barr or herpes simplex virus, was associated with increased risk of active tuberculosis disease up to 10 years before diagnosis. Individuals with medium HCMV IgG were 2.8 times more likely to have tuberculosis (P = .055), and those with high HCMV IgG 3.4 times more likely to have tuberculosis (P = .007). Mycobacterial antibody levels were not associated with differences in odds of tuberculosis disease. Interferon-induced protein 10 was independently associated with increased odds of tuberculosis (odds ratio, 4.2; P = .009).
These data provide evidence of a dose response between magnitude of HCMV IgG with risk of tuberculosis disease. An inflammatory environment, characterized by serum interferon-induced protein 10 and interleukin 1α, is independently associated with increased risk of tuberculosis disease.
最近的证据强调了人类巨细胞病毒（HCMV）和免疫激活是结核病发病的危险因素。目前尚不清楚其他疱疹病毒是否也与此相关，也不清楚结核病风险与疱疹合并感染之间是否存在剂量反应关系。
这项嵌套病例对照研究使用了来自乌干达农村队列中 25 名结核病患者在发病前长达 10 年以及 3 至 6 名无结核病匹配对照者的储存血清样本。研究调查了 Epstein-Barr 病毒、单纯疱疹病毒和 HCMV 特异性免疫球蛋白 G（IgG）、血清炎症标志物和分枝杆菌抗体水平。
针对 HCMV 的体液反应，但不是针对 Epstein-Barr 或单纯疱疹病毒的体液反应，与发病前长达 10 年的活动性结核病发病风险增加相关。HCMV IgG 中等水平的个体发生结核病的可能性增加 2.8 倍（P =.055），HCMV IgG 高水平的个体发生结核病的可能性增加 3.4 倍（P =.007）。分枝杆菌抗体水平与结核病发病几率的差异无关。干扰素诱导蛋白 10 与结核病发病几率的增加独立相关（比值比，4.2；P =.009）。
这些数据提供了证据表明 HCMV IgG 量与结核病发病风险之间存在剂量反应关系。以血清干扰素诱导蛋白 10 和白细胞介素 1α 为特征的炎症环境与结核病发病几率的增加独立相关。
