title: Profiles of acute cytokine and antibody responses in patients infected with avian influenza A H7N9.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Intensive Care Units, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China; Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Department of Intensive Care Units, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Intensive Care Units, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Danjiang
authors.initials: D
authors.lastname: Dong
authors.affiliation: China-US Vaccine Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zuhu
authors.initials: Z
authors.lastname: Huang
authors.affiliation: China-US Vaccine Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D005334:Fever; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D064766:Influenza A Virus, H7N9 Subtype / Q000145:classification / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood* / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes