title: Association of profoundly impaired immune competence in H1N1v-infected patients with a severe or fatal clinical course.
abstract: BACKGROUND
  Pandemic A/H1N1v influenza is characterized by a mild clinical course. However, a small subset of patients develops a rapidly progressive course caused by primary viral pneumonia or secondary bacterial infections that, in many cases, lead to death due to respiratory failure. The aim of the present study was to analyze the involvement of the immune response in the clinical presentation of H1N1v influenza.
  
  
  METHODS
  The differentiation and functional capability of T cells from H1N1v-infected patients presenting with either mild disease (n=22) or severe or fatal disease (n=6) were compared. Moreover, plasma cytokines and chemokines were quantified.
  
  
  RESULTS
  T cells from H1N1v-infected patients presenting with a severe clinical course resulted in impaired effector cell differentiation and failed to respond to mitogenic stimulation. T cell anergy was strictly associated with a severe acute phase of infection, but T cells could be restored in patients able to recover. Of interest, massive expression of CD95 marker was found on anergic T cells, suggesting an apoptosis-related mechanism. Finally, lower plasma levels of interferon-alpha and monocyte chemoattractant protein-1 were found in patients with a worse clinical course of influenza, suggesting impaired production of these cytokines.
  
  
  CONCLUSIONS
  Our results show a strict association between host immune competence and the severity of the clinical course of H1N1v infection. By monitoring host functional response, patients with an enhanced risk of developing influenza-associated severe complications could be identified in a timely manner.
authors.affiliation: National Institute for Infectious Diseases Lazzaro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, Via Portuense 292, Rome, Italy. agrati@inmi.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Agrati
authors.forename: Cristiana
authors.initials: C
authors.lastname: Gioia
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lalle
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cimini
authors.forename: Concetta
authors.initials: C
authors.lastname: Castilletti
authors.forename: Orlando
authors.initials: O
authors.lastname: Armignacco
authors.forename: Francesco Nicola
authors.initials: FN
authors.lastname: Lauria
authors.forename: Federica
authors.initials: F
authors.lastname: Ferraro
authors.forename: Mario
authors.initials: M
authors.lastname: Antonini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
authors.forename: Federico
authors.initials: F
authors.lastname: Martini
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology* / Q000821:virology; D016898:Interferon-alpha / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D019014:fas Receptor