Huang Rui, Zhang Lu, Gu Qin, Zhou Yi-Hua, Hao Yingying, Zhang Kui, Liu Yong, Dong Danjiang, Wang Shixia, Huang Zuhu, Lu Shan, Wu Chao
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China; Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; China-US Vaccine Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
PLoS One. 2014 Jul 8;9(7):e101788. doi: 10.1371/journal.pone.0101788. eCollection 2014.
The influenza A H7N9 virus outbreak in Eastern China in the spring of 2013 represented a novel, emerging avian influenza transmission to humans. While clinical and microbiological features of H7N9 infection have been reported in the literature, the current study investigated acute cytokine and antibody responses in acute H7N9 infection. Between March 27, 2013 and April 23, 2013, six patients with confirmed H7N9 influenza infection were admitted to Drum Tower Hospital, Nanjing, China. Acute phase serum cytokine profiles were determined using a high-throughput multiplex assay. Daily H7 hemagglutinin (HA)-specific IgG, IgM, and IgA responses were monitored by ELISA. Neutralizing antibodies specific for H7N9 viruses were determined against a pseudotyped virus expressing the novel H7 subtype HA antigen. Five cytokines (IL-6, IP-10, IL-10, IFNγ, and TNFα) were significantly elevated in H7N9-infected patients when compared to healthy volunteers. Serum H7 HA-specific IgG, as well as IgM and IgA responses, were detected within 8 days of disease onset and increased in a similar pattern during acute infection. Neutralizing antibodies developed shortly after the appearance of binding antibody responses and showed similar kinetics as a fraction of the total H7 HA-specific IgG responses. H7N9 infection resulted in hallmark serum cytokine increases, which correlated with fever and disease persistence. The novel finding of simultaneous development of IgG, IgM, and IgA responses in acute H7N9 infection points to the potential for live influenza viruses to elicit fast and potent protective antibodies to limit the infection.
2013年春季中国东部地区甲型H7N9流感病毒爆发，代表了一种新型的、新出现的禽流感向人类的传播。虽然H7N9感染的临床和微生物学特征已有文献报道，但本研究调查了急性H7N9感染时的急性细胞因子和抗体反应。2013年3月27日至2013年4月23日期间，6例确诊为H7N9流感感染的患者被收治入中国南京鼓楼医院。使用高通量多重检测法测定急性期血清细胞因子谱。通过ELISA监测每日H7血凝素（HA）特异性IgG、IgM和IgA反应。针对表达新型H7亚型HA抗原的假型病毒测定H7N9病毒特异性中和抗体。与健康志愿者相比，H7N9感染患者中有5种细胞因子（IL-6、IP-10、IL-10、IFNγ和TNFα）显著升高。在疾病发作8天内检测到血清H7 HA特异性IgG以及IgM和IgA反应，且在急性感染期间以相似模式增加。中和抗体在结合抗体反应出现后不久产生，并且与总H7 HA特异性IgG反应的一部分表现出相似的动力学。H7N9感染导致血清细胞因子特征性升高，这与发热和疾病持续时间相关。急性H7N9感染中IgG、IgM和IgA反应同时出现这一新发现表明，活流感病毒有可能引发快速且有效的保护性抗体以限制感染。
