Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.
Identifieur interne : 000182 ( PubMed/Corpus ); précédent : 000181; suivant : 000183Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.
Auteurs : 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 ; John V. Williams ; Guillermina A. Melendi ; Fernando P. PolackSource :
- Nature medicine [ 1546-170X ] ; 2011.
English descriptors
- KwdEn :
- Adolescent, Adult, Age Factors, Antibodies, Viral (immunology), Antigen-Antibody Complex (immunology), Antigens, Viral (immunology), Complement C3 (analysis), Cross Reactions (immunology), Cytokines (blood), Humans, Influenza A Virus, H1N1 Subtype (immunology), Influenza, Human (blood), Influenza, Human (immunology), Influenza, Human (pathology), Influenza, Human (virology), Interferon-alpha (blood), Interferon-beta (blood), Lung (immunology), Lung (pathology), Lung (virology), Middle Aged, Young Adult.
- MESH :
- chemical , analysis : Complement C3.
- chemical , blood : Cytokines, Interferon-alpha, Interferon-beta.
- chemical , immunology : Antibodies, Viral, Antigen-Antibody Complex, Antigens, Viral.
- blood : Influenza, Human.
- immunology : Cross Reactions, Influenza A Virus, H1N1 Subtype, Influenza, Human, Lung.
- pathology : Influenza, Human, Lung.
- virology : Influenza, Human, Lung.
- Adolescent, Adult, Age Factors, Humans, Middle Aged, Young Adult.
Abstract
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.
DOI: 10.1038/nm.2262
PubMed: 21131958
Links to Exploration step
pubmed:21131958Le document en format XML
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Krause</name></author><author><name sortKey="Klemenc, Jennifer" sort="Klemenc, Jennifer" uniqKey="Klemenc J" first="Jennifer" last="Klemenc">Jennifer Klemenc</name></author><author><name sortKey="Hernandez, Johanna Zea" sort="Hernandez, Johanna Zea" uniqKey="Hernandez J" first="Johanna Zea" last="Hernandez">Johanna Zea Hernandez</name></author><author><name sortKey="Maskin, Bernardo" sort="Maskin, Bernardo" uniqKey="Maskin B" first="Bernardo" last="Maskin">Bernardo Maskin</name></author><author><name sortKey="Bugna, Jimena" sort="Bugna, Jimena" uniqKey="Bugna J" first="Jimena" last="Bugna">Jimena Bugna</name></author><author><name sortKey="Rubinstein, Carlos" sort="Rubinstein, Carlos" uniqKey="Rubinstein C" first="Carlos" last="Rubinstein">Carlos Rubinstein</name></author><author><name sortKey="Aguilar, Leandro" sort="Aguilar, Leandro" uniqKey="Aguilar L" first="Leandro" last="Aguilar">Leandro Aguilar</name></author><author><name sortKey="Dalurzo, Liliana" sort="Dalurzo, Liliana" uniqKey="Dalurzo L" first="Liliana" last="Dalurzo">Liliana Dalurzo</name></author><author><name sortKey="Libster, Romina" sort="Libster, Romina" uniqKey="Libster R" first="Romina" last="Libster">Romina Libster</name></author><author><name sortKey="Savy, Vilma" sort="Savy, Vilma" uniqKey="Savy V" first="Vilma" last="Savy">Vilma Savy</name></author><author><name sortKey="Baumeister, Elsa" sort="Baumeister, Elsa" uniqKey="Baumeister E" first="Elsa" last="Baumeister">Elsa Baumeister</name></author><author><name sortKey="Aguilar, Liliana" sort="Aguilar, Liliana" uniqKey="Aguilar L" first="Liliana" last="Aguilar">Liliana Aguilar</name></author><author><name sortKey="Cabral, Graciela" sort="Cabral, Graciela" uniqKey="Cabral G" first="Graciela" last="Cabral">Graciela Cabral</name></author><author><name sortKey="Font, Julia" sort="Font, Julia" uniqKey="Font J" first="Julia" last="Font">Julia Font</name></author><author><name sortKey="Solari, Liliana" sort="Solari, Liliana" uniqKey="Solari L" first="Liliana" last="Solari">Liliana Solari</name></author><author><name sortKey="Weller, Kevin P" sort="Weller, Kevin P" uniqKey="Weller K" first="Kevin P" last="Weller">Kevin P. 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Polack</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21131958</idno><idno type="pmid">21131958</idno><idno type="doi">10.1038/nm.2262</idno><idno type="wicri:Area/PubMed/Corpus">000182</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000182</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.</title><author><name sortKey="Monsalvo, Ana Clara" sort="Monsalvo, Ana Clara" uniqKey="Monsalvo A" first="Ana Clara" last="Monsalvo">Ana Clara Monsalvo</name><affiliation><nlm:affiliation>Fundacion INFANT, Buenos Aires, Argentina.</nlm:affiliation></affiliation></author><author><name sortKey="Batalle, Juan P" sort="Batalle, Juan P" uniqKey="Batalle J" first="Juan P" last="Batalle">Juan P. Batalle</name></author><author><name sortKey="Lopez, M Florencia" sort="Lopez, M Florencia" uniqKey="Lopez M" first="M Florencia" last="Lopez">M Florencia Lopez</name></author><author><name sortKey="Krause, Jens C" sort="Krause, Jens C" uniqKey="Krause J" first="Jens C" last="Krause">Jens C. Krause</name></author><author><name sortKey="Klemenc, Jennifer" sort="Klemenc, Jennifer" uniqKey="Klemenc J" first="Jennifer" last="Klemenc">Jennifer Klemenc</name></author><author><name sortKey="Hernandez, Johanna Zea" sort="Hernandez, Johanna Zea" uniqKey="Hernandez J" first="Johanna Zea" last="Hernandez">Johanna Zea Hernandez</name></author><author><name sortKey="Maskin, Bernardo" sort="Maskin, Bernardo" uniqKey="Maskin B" first="Bernardo" last="Maskin">Bernardo Maskin</name></author><author><name sortKey="Bugna, Jimena" sort="Bugna, Jimena" uniqKey="Bugna J" first="Jimena" last="Bugna">Jimena Bugna</name></author><author><name sortKey="Rubinstein, Carlos" sort="Rubinstein, Carlos" uniqKey="Rubinstein C" first="Carlos" last="Rubinstein">Carlos Rubinstein</name></author><author><name sortKey="Aguilar, Leandro" sort="Aguilar, Leandro" uniqKey="Aguilar L" first="Leandro" last="Aguilar">Leandro Aguilar</name></author><author><name sortKey="Dalurzo, Liliana" sort="Dalurzo, Liliana" uniqKey="Dalurzo L" first="Liliana" last="Dalurzo">Liliana Dalurzo</name></author><author><name sortKey="Libster, Romina" sort="Libster, Romina" uniqKey="Libster R" first="Romina" last="Libster">Romina Libster</name></author><author><name sortKey="Savy, Vilma" sort="Savy, Vilma" uniqKey="Savy V" first="Vilma" last="Savy">Vilma Savy</name></author><author><name sortKey="Baumeister, Elsa" sort="Baumeister, Elsa" uniqKey="Baumeister E" first="Elsa" last="Baumeister">Elsa Baumeister</name></author><author><name sortKey="Aguilar, Liliana" sort="Aguilar, Liliana" uniqKey="Aguilar L" first="Liliana" last="Aguilar">Liliana Aguilar</name></author><author><name sortKey="Cabral, Graciela" sort="Cabral, Graciela" uniqKey="Cabral G" first="Graciela" last="Cabral">Graciela Cabral</name></author><author><name sortKey="Font, Julia" sort="Font, Julia" uniqKey="Font J" first="Julia" last="Font">Julia Font</name></author><author><name sortKey="Solari, Liliana" sort="Solari, Liliana" uniqKey="Solari L" first="Liliana" last="Solari">Liliana Solari</name></author><author><name sortKey="Weller, Kevin P" sort="Weller, Kevin P" uniqKey="Weller K" first="Kevin P" last="Weller">Kevin P. Weller</name></author><author><name sortKey="Johnson, Joyce" sort="Johnson, Joyce" uniqKey="Johnson J" first="Joyce" last="Johnson">Joyce Johnson</name></author><author><name sortKey="Echavarria, Marcela" sort="Echavarria, Marcela" uniqKey="Echavarria M" first="Marcela" last="Echavarria">Marcela Echavarria</name></author><author><name sortKey="Edwards, Kathryn M" sort="Edwards, Kathryn M" uniqKey="Edwards K" first="Kathryn M" last="Edwards">Kathryn M. Edwards</name></author><author><name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D" last="Chappell">James D. Chappell</name></author><author><name sortKey="Crowe, James E" sort="Crowe, James E" uniqKey="Crowe J" first="James E" last="Crowe">James E. Crowe</name></author><author><name sortKey="Williams, John V" sort="Williams, John V" uniqKey="Williams J" first="John V" last="Williams">John V. Williams</name></author><author><name sortKey="Melendi, Guillermina A" sort="Melendi, Guillermina A" uniqKey="Melendi G" first="Guillermina A" last="Melendi">Guillermina A. Melendi</name></author><author><name sortKey="Polack, Fernando P" sort="Polack, Fernando P" uniqKey="Polack F" first="Fernando P" last="Polack">Fernando P. Polack</name></author></analytic><series><title level="j">Nature medicine</title><idno type="eISSN">1546-170X</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age Factors</term><term>Antibodies, Viral (immunology)</term><term>Antigen-Antibody Complex (immunology)</term><term>Antigens, Viral (immunology)</term><term>Complement C3 (analysis)</term><term>Cross Reactions (immunology)</term><term>Cytokines (blood)</term><term>Humans</term><term>Influenza A Virus, H1N1 Subtype (immunology)</term><term>Influenza, Human (blood)</term><term>Influenza, Human (immunology)</term><term>Influenza, Human (pathology)</term><term>Influenza, Human (virology)</term><term>Interferon-alpha (blood)</term><term>Interferon-beta (blood)</term><term>Lung (immunology)</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Middle Aged</term><term>Young Adult</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Complement C3</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Cytokines</term><term>Interferon-alpha</term><term>Interferon-beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Viral</term><term>Antigen-Antibody Complex</term><term>Antigens, Viral</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cross Reactions</term><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza, Human</term><term>Lung</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Influenza, Human</term><term>Lung</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Influenza, Human</term><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age Factors</term><term>Humans</term><term>Middle Aged</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21131958</PMID><DateCompleted><Year>2011</Year><Month>03</Month><Day>18</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1546-170X</ISSN><JournalIssue CitedMedium="Internet"><Volume>17</Volume><Issue>2</Issue><PubDate><Year>2011</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Nature medicine</Title><ISOAbbreviation>Nat. Med.</ISOAbbreviation></Journal><ArticleTitle>Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.</ArticleTitle><Pagination><MedlinePgn>195-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/nm.2262</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Monsalvo</LastName><ForeName>Ana Clara</ForeName><Initials>AC</Initials><AffiliationInfo><Affiliation>Fundacion INFANT, Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Batalle</LastName><ForeName>Juan P</ForeName><Initials>JP</Initials></Author><Author ValidYN="Y"><LastName>Lopez</LastName><ForeName>M Florencia</ForeName><Initials>MF</Initials></Author><Author ValidYN="Y"><LastName>Krause</LastName><ForeName>Jens C</ForeName><Initials>JC</Initials></Author><Author ValidYN="Y"><LastName>Klemenc</LastName><ForeName>Jennifer</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Hernandez</LastName><ForeName>Johanna Zea</ForeName><Initials>JZ</Initials></Author><Author ValidYN="Y"><LastName>Maskin</LastName><ForeName>Bernardo</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Bugna</LastName><ForeName>Jimena</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Rubinstein</LastName><ForeName>Carlos</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Aguilar</LastName><ForeName>Leandro</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Dalurzo</LastName><ForeName>Liliana</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Libster</LastName><ForeName>Romina</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Savy</LastName><ForeName>Vilma</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Baumeister</LastName><ForeName>Elsa</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Aguilar</LastName><ForeName>Liliana</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Cabral</LastName><ForeName>Graciela</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Font</LastName><ForeName>Julia</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Solari</LastName><ForeName>Liliana</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Weller</LastName><ForeName>Kevin P</ForeName><Initials>KP</Initials></Author><Author ValidYN="Y"><LastName>Johnson</LastName><ForeName>Joyce</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Echavarria</LastName><ForeName>Marcela</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Edwards</LastName><ForeName>Kathryn M</ForeName><Initials>KM</Initials></Author><Author ValidYN="Y"><LastName>Chappell</LastName><ForeName>James D</ForeName><Initials>JD</Initials></Author><Author ValidYN="Y"><LastName>Crowe</LastName><ForeName>James E</ForeName><Initials>JE</Initials><Suffix>Jr</Suffix></Author><Author ValidYN="Y"><LastName>Williams</LastName><ForeName>John V</ForeName><Initials>JV</Initials></Author><Author ValidYN="Y"><LastName>Melendi</LastName><ForeName>Guillermina A</ForeName><Initials>GA</Initials></Author><Author ValidYN="Y"><LastName>Polack</LastName><ForeName>Fernando P</ForeName><Initials>FP</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI054952-05</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R24 TW007988</GrantID><Acronym>TW</Acronym><Agency>FIC NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AI054952</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI054952</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 AI058113</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>12</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Nat Med</MedlineTA><NlmUniqueID>9502015</NlmUniqueID><ISSNLinking>1078-8956</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000936">Antigen-Antibody Complex</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000956">Antigens, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003176">Complement C3</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016898">Interferon-alpha</NameOfSubstance></Chemical><Chemical><RegistryNumber>77238-31-4</RegistryNumber><NameOfSubstance UI="D016899">Interferon-beta</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000367" MajorTopicYN="N">Age Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000936" MajorTopicYN="N">Antigen-Antibody Complex</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000956" MajorTopicYN="N">Antigens, Viral</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003176" MajorTopicYN="N">Complement C3</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003429" MajorTopicYN="N">Cross Reactions</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016207" 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