Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

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

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

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

Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina

Fil: Libster, Romina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Coviello, Silvina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Hijano, Diego R. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Dunaiewsky, Mariana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Reynoso, Natalia. Hospital Municipal Materno Infantil de San Isidro; Argentina.Fil: Cavalieri, Maria L. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Guglielmo, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Areso, M. Soledad. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Gilligan, Tomas. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santucho, Fernanda. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Gregorio, Gabriela L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Moreno, Rina. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Lutz, Maria I. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Panigasi, Alicia L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Saligari, Liliana. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Caballero, Mauricio T. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Egües Almeida, Rodrigo M. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Gutierrez Meyer, Maria E. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Neder, Maria D. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Davenport, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Del Valle, Maria P. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santidrian, Valeria S. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Mosca, Guillermina. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alvarez, Liliana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Landa, Patricia. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Pota, Ana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Boloñati, Norma. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Dalamon, Ricardo. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Sanchez Mercol, Victoria I. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Espinoza, Marco. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Peuchot, Juan Carlos. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Karolinski, Ariel. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bruno, Miriam. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Borsa, Ana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Ferrero, Fernando. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bonina, Angel. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Ramonet, Margarita. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Albano, Lidia C. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Luedicke, Nora. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alterman, Elias. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Savy, Vilma L. ANLIS Dr.C.G.Malbrán. Instituto de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Virosis Respiratoria; Argentina.Fil: Chappell, James D. Vanderbilt University. Pathology, Nashville, Tennessee; Estados Unidos.Fil: Edwards, Kathryn M. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Melendi, Guillermina A. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Polack, Fernando P. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Background: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. Methods: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. Results: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). Conclusions: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years

T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children

Background: The immune response to dengue virus (DENV) primary infection in infants and young children is not well characterized. In Northern Argentina, .90% of the population was DENV-naı¨ve before the 2009 outbreak, allowing evaluation of age-dependent primary responses to infection. Methods: We conducted a comparative study of the immune response to DENV in 27 infected infants, young children and their mothers. Lymphocyte T helper (Th) 1, Th2, Th17 and inflammatory responses were assayed in blood during the 2009 DENV-1 epidemic. Results: The immune response to DENV-1 was significantly biased to Th2 in infected infants and young children, compared to infants with other febrile illnesses (for IL-4 p,0.001) and to their infected mothers (for IL-4 p,0.01). In addition, IL-17 suppression was observed in the memory response to DENV-1 in infected infants (p,0.01 vs placebo). Conclusion: Age-related differences in the primary response to DENV, characterized by an immature Th2 polarization and Th17 suppression in infants, should be studied further in order to expand our understanding of the mechanism of dengue pathogenesis.Fil: Talarico, Laura Beatriz. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bugna Hortoneda, Jimena. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Wimmenauer, Vera. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Espinoza, Marco A.. Hospital San Vicente de Paul; ArgentinaFil: Quipildor, Marcelo O.. Hospital San Vicente de Paul; ArgentinaFil: Hijano, Diego R.. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Beccaria, Martín. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Wurster, Victoria. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Cavagnaro, Luis E.. Hospital SAMIC Iguazu; ArgentinaFil: Martinez, Daniel. Hospital SAMIC Iguazu; ArgentinaFil: Fattore, Gladys. Fundación Mundo Sano; ArgentinaFil: Batalle, Juan Pio. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reynoso, Natalia. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Melendi, Guillermina Amanda. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Rey, Felix A.. Institut Pasteur. Département de Virologie. Unité de Virologie Structurale; FranciaFil: Libster, Romina Paula. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polack, Fernando Pedro. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

MAcronutrients during pregnancy and life-threatening respiratory syncytial virus infections in children

Rationale: Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. Objectives: We defined the burden of life-threatening (O2 saturation [O2 sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children’s pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. Methods: Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O2 sat less than 93% on admission were included. Measurements and Main Results: Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5–2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV+), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4–1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15–9.44] to 7.36 [95% CI, 2.41–22.5] versus the lowest quartile). Conclusions: Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes.Fil: Ferolla, Fausto Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Hijano, Diego Raúl. Fundación para la Investigación en Infectologia Infantil; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rodríguez, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos Descentralizado “Evita Pueblo"; ArgentinaFil: Dueñas, Karina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Sancilio, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Barboza, Edgar. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Narciso López"; ArgentinaFil: Caría, Adriana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Narciso López"; ArgentinaFil: Fernández Gago, Guadalupe. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Egües Almeida, Rodrigo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Castro, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Pozzolo, Cecilia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal de Agudos "Dr. Arturo Oñativia"; ArgentinaFil: Martínez, María V.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Lucio Meléndez”; ArgentinaFil: Grimaldi Alva, Luciano. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Lucio Meléndez”; ArgentinaFil: Rebec, Beatriz. Provinicia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Presidente Perón”; ArgentinaFil: Calvo, Mariel. Provinicia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Presidente Perón"; ArgentinaFil: Henrichsen, Julieta. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Dr. Pedro Fiorito”; ArgentinaFil: Nocito, Celina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Dr. Pedro Fiorito”; ArgentinaFil: González, Mariela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Alberto Eurnekián"; ArgentinaFil: Barbero, Guillermo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Ves Losada, Juan. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Zurankovas, Valeria. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Raggio, Mirta. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Schavlovsky, Graciela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Kobylarz, Alicia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Materno Infantil “Ana Goitia”; ArgentinaFil: Wimmenauer, Vera. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bugna, Jimena. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Williams, John V.. Vanderbilt University; Estados UnidosFil: Sastre, Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Flamenco, Edgardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal de Agudos "Dr. Arturo Oñativia"; ArgentinaFil: Rodríguez Pérez, Alberto. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Alberto Eurnekián"; ArgentinaFil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Libster, Romina Paula. Vanderbilt University; Estados Unidos. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Grijalva, Carlos G.. Vanderbilt University; Estados UnidosFil: Polack, Fernando Pedro. Vanderbilt University; Estados Unidos. Fundación para la Investigación en Infectología Infantil; Argentin

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

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 understood1–10. 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