HMGB1 Is a Potential Biomarker for Severe Viral Hemorrhagic Fevers

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. Infection with Dobrava or Puumala virus (HFRS) and Crimean-Congo hemorrhagic fever virus (CCHFV) can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. An important factor in optimizing survival rate in patients with VHF is instant recognition of the severe form of the disease for which significant biomarkers need to be elucidated. To determine the prognostic value of High Mobility Group Box 1 (HMGB1) as a biomarker for disease severity, we tested acute serum samples of patients with HFRS or CCHF. Our results showed that HMGB1 levels are increased in patients with CCHFV, DOBV or PUUV infection. Above that, concentration of HMGB1 is higher in patients with severe disease progression when compared to the mild clinical course of the disease. Our results indicate that HMGB1 could be a useful prognostic biomarker for disease severity in PUUV and CCHFV infection, where the difference between the mild and severe patients group was highly significant. Even in patients with severe DOBV infection concentrations of HMGB1 were 2.8–times higher than in the mild group, but the difference was not statistically significant. Our results indicated HMGB1 as a potential biomarker for severe hemorrhagic fevers.

肾综合征出血热（Hemorrhagic fever with renal syndrome, HFRS）与克里米亚-刚果出血热（Crimean-Congo hemorrhagic fever, CCHF）是病毒性出血热的常见代表类型，目前在全球部分地区仍常被忽视。感染多布拉瓦病毒（Dobrava virus, DOBV）或普马拉病毒（Puumala virus, PUUV，二者均为肾综合征出血热的致病原）、克里米亚-刚果出血热病毒（Crimean-Congo hemorrhagic fever virus, CCHFV）后，患者可表现为轻症非特异性发热性疾病，亦可进展为伴出血的重症病症，且病死率较高。优化病毒性出血热（Viral hemorrhagic fever, VHF）患者生存率的关键环节之一，是及时识别重症病例，而这亟需阐明相关关键生物标志物。为明确高迁移率族蛋白B1（High Mobility Group Box 1, HMGB1）作为疾病严重程度生物标志物的预后价值，我们检测了肾综合征出血热或克里米亚-刚果出血热患者的急性血清样本。结果显示，感染CCHFV、DOBV或PUUV的患者体内HMGB1水平均升高。此外，与轻症病程患者相比，病情进展为重症的患者其HMGB1浓度更高。研究结果表明，HMGB1可作为PUUV及CCHFV感染患者疾病严重程度的有效预后生物标志物，两组轻症与重症患者的HMGB1水平差异具有高度统计学意义。即便在重症DOBV感染患者中，其HMGB1浓度也较轻症组升高2.8倍，但该差异未达到统计学显著性。本研究结果提示，HMGB1可作为重症病毒性出血热的潜在生物标志物。