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Title: Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes
Authors: Monsalvo, Ana Clara 
Batalle, Juan P. 
Lopez, M. Florencia 
Krause, Jens C. 
Klemenc, Jennifer 
Zea, Johanna 
Maskin, Bernardo 
Bugna, Jimena 
Rubinstein, Carlos 
Aguilar, Leandro 
Dalurzo, Liliana 
Libster, Romina 
Savy, Vilma L. 
Baumeister, Elsa 
Aguilar, Liliana 
Cabral, Graciela 
Font, Julia 
Solari, Liliana 
Weller, Kevin P. 
Johnson, Joyce 
Echavarria, Marcela 
Edwards, Kathryn M. 
Chappell, James D. 
Crowe, James E. 
Williams, John V. 
Melendi, Guillermina A. 
Polack, Fernando P. 
Issue Date: 2011
Description: Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood–. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics.
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Rights: openAccess
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