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Nature. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes
Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes (Nature, abstract, edited)
[Source: Nature, full page: <cite cite="http://www.nature.com/nm/journal/v17/n2/full/nm.2262.html">Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes : Nature Medicine : Nature Publishing Group</cite>. Abstract, edited.]
Nature Medicine | Letter
Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes
* Ana Clara Monsalvo, * Juan P Batalle, * M Florencia Lopez, * Jens C Krause, * Jennifer Klemenc, * Johanna Zea Hernandez, * Bernardo Maskin, * Jimena Bugna, * Carlos Rubinstein, * Leandro Aguilar, * Liliana Dalurzo, * Romina Libster, * Vilma Savy, * Elsa Baumeister, * Liliana Aguilar, * Graciela Cabral, * Julia Font, * Liliana Solari, * Kevin P Weller, * Joyce Johnson, * Marcela Echavarria, * Kathryn M Edwards, * James D Chappell, * James E Crowe Jr, * John V Williams, * Guillermina A Melendi * & Fernando P Polack * et al.
Journal name: Nature Medicine
Volume: 17, Pages: 195?199
Year published: (2011)
DOI: doi:10.1038/nm.2262
Received 19 May 2010
Accepted 19 October 2010
Published online 05 December 2010
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 understood1, 2, 3, 4, 5, 6, 7, 8, 9, 10. 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.
Author information
1. These authors contributed equally to this work. * Ana Clara Monsalvo, * Juan P Batalle & * M Florencia Lopez
Affiliations
1. Fundacion INFANT, Buenos Aires, Argentina. * Ana Clara Monsalvo, * Juan P Batalle, * M Florencia Lopez, * Johanna Zea Hernandez, * Jimena Bugna, * Romina Libster, * Guillermina A Melendi & * Fernando P Polack
2. Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA. * Jens C Krause, * Jennifer Klemenc, * Johanna Zea Hernandez, * Kevin P Weller, * Kathryn M Edwards, * James E Crowe Jr, * John V Williams, * Guillermina A Melendi & * Fernando P Polack
3. Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina. * Bernardo Maskin, * Liliana Aguilar, * Graciela Cabral, * Julia Font & * Liliana Solari
4. Hospital Dr. Federico Abete, Malvinas Argentinas, Buenos Aires, Argentina. * Carlos Rubinstein & * Leandro Aguilar
5. Hospital Italiano, Buenos Aires, Argentina. * Liliana Dalurzo
6. Administraci?n Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina. * Vilma Savy & * Elsa Baumeister
7. Department of Pathology, Vanderbilt University, Nashville, Tennessee, USA. * Joyce Johnson & * James D Chappell
8. Department of Microbiology, Centro de Educaci?n M?dica e Investigaciones Cl?nicas, Buenos Aires, Argentina. * Marcela Echavarria
Contributions
F.P.P., G.A.M., K.M.E., J.D.C., J.E.C. Jr., J.V.W., A.C.M., J.P.B. and M.F.L. designed the project. A.C.M., J.P.B., M.F.L., J.Z.H., B.M., L.D., K.P.W., J.V.W., G.A.M. and F.P.P. performed experiments. J.C.K., J.K., J.B., C.R., Le. A., L.D., R.L., V.S., E.B., Li. A., G.C., J.F., L.S., J.J., M.E., J.E.C. Jr. and J.V.W. developed or provided key reagents or contributed samples. F.P.P. supervised the project. A.C.M., J.P.B., M.F.L., K.M.E., J.D.C., G.A.M. and F.P.P. wrote the paper.
Competing financial interests
The authors declare no competing financial interests.
Corresponding authors
Correspondence to: * Fernando P Polack or * Guillermina A Melendi
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[Source: Nature, full page: <cite cite="http://www.nature.com/nm/journal/v17/n2/full/nm.2262.html">Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes : Nature Medicine : Nature Publishing Group</cite>. Abstract, edited.]
Nature Medicine | Letter
Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes
* Ana Clara Monsalvo, * Juan P Batalle, * M Florencia Lopez, * Jens C Krause, * Jennifer Klemenc, * Johanna Zea Hernandez, * Bernardo Maskin, * Jimena Bugna, * Carlos Rubinstein, * Leandro Aguilar, * Liliana Dalurzo, * Romina Libster, * Vilma Savy, * Elsa Baumeister, * Liliana Aguilar, * Graciela Cabral, * Julia Font, * Liliana Solari, * Kevin P Weller, * Joyce Johnson, * Marcela Echavarria, * Kathryn M Edwards, * James D Chappell, * James E Crowe Jr, * John V Williams, * Guillermina A Melendi * & Fernando P Polack * et al.
Journal name: Nature Medicine
Volume: 17, Pages: 195?199
Year published: (2011)
DOI: doi:10.1038/nm.2262
Received 19 May 2010
Accepted 19 October 2010
Published online 05 December 2010
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 understood1, 2, 3, 4, 5, 6, 7, 8, 9, 10. 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.
Author information
1. These authors contributed equally to this work. * Ana Clara Monsalvo, * Juan P Batalle & * M Florencia Lopez
Affiliations
1. Fundacion INFANT, Buenos Aires, Argentina. * Ana Clara Monsalvo, * Juan P Batalle, * M Florencia Lopez, * Johanna Zea Hernandez, * Jimena Bugna, * Romina Libster, * Guillermina A Melendi & * Fernando P Polack
2. Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA. * Jens C Krause, * Jennifer Klemenc, * Johanna Zea Hernandez, * Kevin P Weller, * Kathryn M Edwards, * James E Crowe Jr, * John V Williams, * Guillermina A Melendi & * Fernando P Polack
3. Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina. * Bernardo Maskin, * Liliana Aguilar, * Graciela Cabral, * Julia Font & * Liliana Solari
4. Hospital Dr. Federico Abete, Malvinas Argentinas, Buenos Aires, Argentina. * Carlos Rubinstein & * Leandro Aguilar
5. Hospital Italiano, Buenos Aires, Argentina. * Liliana Dalurzo
6. Administraci?n Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina. * Vilma Savy & * Elsa Baumeister
7. Department of Pathology, Vanderbilt University, Nashville, Tennessee, USA. * Joyce Johnson & * James D Chappell
8. Department of Microbiology, Centro de Educaci?n M?dica e Investigaciones Cl?nicas, Buenos Aires, Argentina. * Marcela Echavarria
Contributions
F.P.P., G.A.M., K.M.E., J.D.C., J.E.C. Jr., J.V.W., A.C.M., J.P.B. and M.F.L. designed the project. A.C.M., J.P.B., M.F.L., J.Z.H., B.M., L.D., K.P.W., J.V.W., G.A.M. and F.P.P. performed experiments. J.C.K., J.K., J.B., C.R., Le. A., L.D., R.L., V.S., E.B., Li. A., G.C., J.F., L.S., J.J., M.E., J.E.C. Jr. and J.V.W. developed or provided key reagents or contributed samples. F.P.P. supervised the project. A.C.M., J.P.B., M.F.L., K.M.E., J.D.C., G.A.M. and F.P.P. wrote the paper.
Competing financial interests
The authors declare no competing financial interests.
Corresponding authors
Correspondence to: * Fernando P Polack or * Guillermina A Melendi
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