Fil: Monsalvo, Ana Clara. Fundacion INFANT, Buenos Aires; Argentina.Fil: Batalle, Juan P. Fundacion INFANT, Buenos Aires; Argentina.Fil: Lopez, M Florencia. Fundacion INFANT, Buenos Aires; Argentina.Fil: Krause, Jens C. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Klemenc, Jennifer. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Hernandez, Johanna Zea. . Fundacion INFANT, Buenos Aires; Argentina.Fil: Maskin, Bernardo. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundacion INFANT, Buenos Aires; Argentina.Fil: Rubinstein, Carlos. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Aguilar, Leandro. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Dalurzo, Liliana. Hospital Italiano, Buenos Aires; Argentina.Fil: Libster, Romina. Fundacion INFANT, Buenos Aires; Argentina.Fil: Savy, Vilma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Aguilar, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Font, Julia. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Solari, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Weller, Kevin P. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Johnson, Joyce. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Echavarria, Marcela. Department of Microbiology, CEMIC, Buenos Aires; Argentina.Fil: Edwards, Kathryn M. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Chappell, James D. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Crowe, James E. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Williams, John V. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Melendi, Guillermina A. Fundacion INFANT, Buenos Aires; Argentina.Fil: Polack, Fernando P. Fundacion INFANT, Buenos Aires; Argentina.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
