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

Monsalvo AC, Batalle JP, Lopez MF, Krause JC, Klemenc J, Hernandez JZ, Maskin B, Bugna J, Rubinstein C, Aguilar L, Dalurzo L, Libster R, Savy V, Baumeister E, Aguilar L, Cabral G, Font J, Solari L, Weller KP, Johnson J, Echavarria M, Edwards KM, Chappell JD, Crowe JE, Williams JV, Melendi GA, Polack FP
Nat Med. 2011 17 (2): 195-9

PMID: 21131958 · PMCID: PMC3034774 · DOI:10.1038/nm.2262

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.

MeSH Terms (17)

Adolescent Adult Age Factors Antibodies, Viral Antigen-Antibody Complex Antigens, Viral Complement C3 Cross Reactions Cytokines Humans Influenza, Human Influenza A Virus, H1N1 Subtype Interferon-alpha Interferon-beta Lung Middle Aged Young Adult

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