title: Serum and mucosal antibodies fail as prognostic markers during critical influenza A infection.
abstract: BACKGROUND
  Previous studies have indicated that the absence of serum antibodies to influenza A H1N1 virus on day 4 after onset of symptoms predicted a fatal outcome in patients critically ill with influenza. The underlying mechanism was suggested to be the trapping of anti-influenza antibodies in pulmonary immune complexes.
  
  
  OBJECTIVE
  To study serum and mucosal antibodies as prognostic markers in patients with severe influenza A H1N1 infection.
  
  
  METHODS
  Blood and respiratory samples (n=324) from 12 patients with severe influenza were analysed for anti-H1N1 antibodies with and without immune complex dissociation from symptom onset until convalescence or death (follow up 14-169 days). Eleven healthy subjects were analysed for comparison.
  
  
  RESULTS
  One of the 12 patients died from influenza pneumonia and had no detectable anti-H1N1 serum antibodies. However, also 2 of the 11 surviving patients remained negative for anti-H1N1 serum antibodies during follow-up (20 and 41 days, respectively). In six of the 11 survivors serum antibodies on day 4 were negative, but turned positive between day 7 and 23. In the remaining 3 patients antibodies were detected in the first 4 days of illness. Mucosal IgG or IgA was detected in all of the patients regardless of their clinical outcome and in 4 of 11 healthy subjects. No mucosal immune complexes were found in the patient who died but were detected in 3 of the 11 survivors.
  
  
  CONCLUSIONS
  This study suggests that no prognostic conclusions can be drawn from anti-H1N1 serum and mucosal antibodies in patients with severe influenza.
authors.affiliation: University of Düsseldorf, Medical Faculty, Institute for Virology, D-40225 Düsseldorf, Germany. Electronic address: sebastian.grund@med.uni-duesseldorf.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grund
authors.affiliation: University of Düsseldorf, Medical Faculty, Institute for Virology, D-40225 Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michel
authors.affiliation: University of Düsseldorf, Medical Faculty, Institute for Clinical Chemistry, D-40225 Düsseldorf, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Barthuber
authors.affiliation: University of Düsseldorf, Medical Faculty, Institute for Virology, D-40225 Düsseldorf, Germany.
authors.forename: Ortwin
authors.initials: O
authors.lastname: Adams
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044967:Serum / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers
keywords: Antibodies; Immune complexes; Influenza; Mucosal antibodies; Prognostic markers