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Nat Med. 2011 Feb;17(2):195-9. doi: 10.1038/nm.2262. Epub 2010 Dec 5.

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.

Author information

1
Fundacion INFANT, Buenos Aires, Argentina.

Abstract

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics.

PMID:
21131958
PMCID:
PMC3034774
DOI:
10.1038/nm.2262
[Indexed for MEDLINE]
Free PMC Article

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