McElroy Anita K, Harmon Jessica R, Flietstra Timothy D, Campbell Shelley, Mehta Aneesh K, Kraft Colleen S, Lyon Marshall G, Varkey Jay B, Ribner Bruce S, Kratochvil Christopher J, Iwen Peter C, Smith Philip W, Ahmed Rafi, Nichol Stuart T, Spiropoulou Christina F
Viral Special Pathogens Branch, US Centers for Disease Control and Prevention Division of Pediatric Infectious Disease.
Viral Special Pathogens Branch, US Centers for Disease Control and Prevention.
Clin Infect Dis. 2016 Aug 15;63(4):460-7. doi: 10.1093/cid/ciw334. Epub 2016 Jun 27.
Ebola virus (EBOV) infection causes a severe and often fatal disease. Despite the fact that more than 30 000 individuals have acquired Ebola virus disease (EVD), the medical and scientific community still does not have a clear understanding of the mechanisms by which EBOV causes such severe disease.
In this study, 54 biomarkers in plasma samples serially collected from 7 patients with EVD were analyzed in an attempt to define the kinetics of inflammatory modulators. Two clinical disease groups were defined (moderate and severe) based on the need for clinical support. Biomarkers were evaluated for correlation with viremia and clinical disease in an effort to identify pathways that could be useful targets of therapeutic intervention.
Patients with severe disease had higher viremia than those with moderate disease. Several biomarkers of immune activation and control were significantly elevated in patients with moderate disease. A series of pro-inflammatory cytokines and chemokines were significantly elevated in patients with severe disease.
Biomarkers that were associated with severe EVD were proinflammatory and indicative of endothelial or coagulation cascade dysfunction, as has been seen historically in patients with fatal outcomes. In contrast, biomarkers that were associated with moderate EVD were suggestive of a strong interferon response and control of both innate and adaptive responses. Therefore, clinical interventions that modulate the phenotype and magnitude of immune activation may be beneficial in treating EVD.
埃博拉病毒（EBOV）感染会引发一种严重且往往致命的疾病。尽管已有超过3万人感染埃博拉病毒病（EVD），但医学界和科学界仍未清楚了解EBOV导致如此严重疾病的机制。
在本研究中，对从7例EVD患者连续采集的血浆样本中的54种生物标志物进行了分析，以试图确定炎症调节因子的动力学。根据临床支持需求定义了两个临床疾病组（中度和重度）。评估生物标志物与病毒血症和临床疾病的相关性，以确定可能成为治疗干预有用靶点的途径。
重度疾病患者的病毒血症高于中度疾病患者。中度疾病患者中几种免疫激活和调控的生物标志物显著升高。重度疾病患者中一系列促炎细胞因子和趋化因子显著升高。
与严重EVD相关的生物标志物具有促炎作用，表明存在内皮或凝血级联功能障碍，这在历史上有致命结局的患者中也曾出现过。相比之下，与中度EVD相关的生物标志物提示存在强烈的干扰素反应以及对固有和适应性反应的调控。因此，调节免疫激活的表型和程度的临床干预措施可能对治疗EVD有益。
