title: Excessive innate immune response and mutant D222G/N in severe A (H1N1) pandemic influenza.
abstract: OBJECTIVE
  Explore the role of viral factors and immune response in patients with severe pandemic pdmH1N1 illness without significant co-morbidity.
  
  
  METHODS
  Seven patients with pdmH1N1 influenza, bilateral chest X-rays infiltrates, requiring mechanical ventilator support were consecutively recruited. Seven age- and gender-matched healthy individuals served as controls.
  
  
  RESULTS
  Four patients were viremic, two with the mutant D222G/N pdmH1N1.Microarray analyses of peripheral blood leukocytes suggested a marked granulocytes activation, but no up-regulation of inflammatory cytokine mRNA. Patients with severe pdmH1NI had a marked systemic complement activation, and in contrast to the lack of cytokine mRNA up-regulation in blood leukocytes, plasma levels of a broad range of inflammatory mediators, including IP-10, and mediators involved in pulmonary remodelling were markedly elevated. Patients with mutant virus had particularly high IP-10 levels, and the most pronounced complement activation.
  
  
  CONCLUSIONS
  In severe pdmH1N1, viremia was common and the D222G/N mutant was found in half of the viremic patients. Host immune response was characterized by strong activation of the innate immune system, including complement and granulocytes activation, increased serum levels of inflammation and pulmonary remodelling markers, possibly contributing to the observed tissue damage. However, few patients were included and further studies are needed to characterize the immune response in severe pdmH1N1 infection.
authors.affiliation: Department of Infectious Diseases, Akershus University Hospital, University of Oslo, Nordbyhagen 1474, Lorenskog, Norway. jan.erik.berdal@ahus.no
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Berdal
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Torgun
authors.initials: T
authors.lastname: Wæhre
authors.forename: Ole K
authors.initials: OK
authors.lastname: Olstad
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Jon H
authors.initials: JH
authors.lastname: Laake
authors.forename: May T
authors.initials: MT
authors.lastname: Furuseth
authors.forename: Anne
authors.initials: A
authors.lastname: Maagaard
authors.forename: Harald
authors.initials: H
authors.lastname: Kjekshus
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Christine M
authors.initials: CM
authors.lastname: Jonassen
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D003165:Complement System Proteins; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics*; D011446:Prospective Studies; D013902:Radiography, Thoracic; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000453:epidemiology / Q000473:pathology; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics*; D014766:Viremia / Q000453:epidemiology
chemical_list: D016207:Cytokines; D014764:Viral Proteins; D003165:Complement System Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase