Association of profoundly impaired immune competence in H1N1v-infected patients with a severe or fatal clinical course.
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.
Agrati
Chiara
C
National Institute for Infectious Diseases Lazzaro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, Via Portuense 292, Rome, Italy. agrati@inmi.it
Gioia
Cristiana
C
Lalle
Eleonora
E
Cimini
Eleonora
E
Castilletti
Concetta
C
Armignacco
Orlando
O
Lauria
Francesco Nicola
FN
Ferraro
Federica
F
Antonini
Mario
M
Ippolito
Giuseppe
G
Capobianchi
Maria Rosaria
MR
Martini
Federico
F
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
D016898:Interferon-alpha; D019014:fas Receptor