Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein
Identifieur interne : 000327 ( Main/Exploration ); précédent : 000326; suivant : 000328Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein
Auteurs : John Woulfe ; Madison T. Gray ; Munisha S. Ganesh ; Jaap M. MiddeldorpSource :
- Neurology® Neuroimmunology & Neuroinflammation [ 2332-7812 ] ; 2016.
Abstract
To identify the epitope on α-synuclein (α-syn) to which antibodies against the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) bind and to determine whether antibodies targeting this mimicry domain are present in human sera.
Reactivity of the α-syn-cross-reacting anti-LMP1 monoclonal antibody CS1-4 to a synthetic peptide containing the putative mimicry domain was compared to those in which this domain was mutated and to murine and rat α-syn (which differ from human α-syn at this site) in Western blots. Using ELISA, sera from EBV+ (n = 4) and EBV− (n = 12) donors as well as those with infectious mononucleosis (IM; n = 120), and Hodgkin disease (HD; n = 33) were interrogated for antibody reactivity to synthetic peptides corresponding to regions of α-syn and LMP1 containing the mimicry domain.
CS1-4 showed strong reactivity to wild-type human α-syn, but not to the mutant peptides or rodent α-syn. Control EBV− and EBV+ sera showed no reactivity to α-syn or LMP1 peptides. However, a significant proportion of IM and HD sera contained immunoglobulin M (IgM) (59% and 70%, in IM and HD, respectively), immunoglobulin G (IgG) (40% and 48%), and immunoglobulin A (IgA) (28% and 36%) antibodies to both peptides, as well as a significant correlation in the titers of IgM (ρ = 0.606 and 0.664, for IM and HD, respectively), IgG (0.526 and 0.836), and IgA (0.569 and 0.728) antibodies targeting LMP1 and α-syn peptides.
Anti-EBV-LMP1 antibodies cross-reacting with a defined epitope in α-syn are present in human patients. These findings may have implications for the pathogenesis of synucleinopathies.
Url:
DOI: 10.1212/NXI.0000000000000239
PubMed: 27218119
PubMed Central: 4864620
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein</title><author><name sortKey="Woulfe, John" sort="Woulfe, John" uniqKey="Woulfe J" first="John" last="Woulfe">John Woulfe</name></author><author><name sortKey="Gray, Madison T" sort="Gray, Madison T" uniqKey="Gray M" first="Madison T." last="Gray">Madison T. Gray</name></author><author><name sortKey="Ganesh, Munisha S" sort="Ganesh, Munisha S" uniqKey="Ganesh M" first="Munisha S." last="Ganesh">Munisha S. Ganesh</name></author><author><name sortKey="Middeldorp, Jaap M" sort="Middeldorp, Jaap M" uniqKey="Middeldorp J" first="Jaap M." last="Middeldorp">Jaap M. Middeldorp</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27218119</idno><idno type="pmc">4864620</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864620</idno><idno type="RBID">PMC:4864620</idno><idno type="doi">10.1212/NXI.0000000000000239</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000146</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000146</idno><idno type="wicri:Area/Pmc/Curation">000146</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000146</idno><idno type="wicri:Area/Pmc/Checkpoint">000111</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000111</idno><idno type="wicri:Area/Ncbi/Merge">001F84</idno><idno type="wicri:Area/Ncbi/Curation">001F84</idno><idno type="wicri:Area/Ncbi/Checkpoint">001F84</idno><idno type="wicri:Area/Main/Merge">000328</idno><idno type="wicri:Area/Main/Curation">000327</idno><idno type="wicri:Area/Main/Exploration">000327</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein</title><author><name sortKey="Woulfe, John" sort="Woulfe, John" uniqKey="Woulfe J" first="John" last="Woulfe">John Woulfe</name></author><author><name sortKey="Gray, Madison T" sort="Gray, Madison T" uniqKey="Gray M" first="Madison T." last="Gray">Madison T. Gray</name></author><author><name sortKey="Ganesh, Munisha S" sort="Ganesh, Munisha S" uniqKey="Ganesh M" first="Munisha S." last="Ganesh">Munisha S. Ganesh</name></author><author><name sortKey="Middeldorp, Jaap M" sort="Middeldorp, Jaap M" uniqKey="Middeldorp J" first="Jaap M." last="Middeldorp">Jaap M. Middeldorp</name></author></analytic><series><title level="j">Neurology® Neuroimmunology & Neuroinflammation</title><idno type="eISSN">2332-7812</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives:</title><p>To identify the epitope on α-synuclein (α-syn) to which antibodies against the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) bind and to determine whether antibodies targeting this mimicry domain are present in human sera.</p></sec><sec><title>Methods:</title><p>Reactivity of the α-syn-cross-reacting anti-LMP1 monoclonal antibody CS1-4 to a synthetic peptide containing the putative mimicry domain was compared to those in which this domain was mutated and to murine and rat α-syn (which differ from human α-syn at this site) in Western blots. Using ELISA, sera from EBV+ (n = 4) and EBV− (n = 12) donors as well as those with infectious mononucleosis (IM; n = 120), and Hodgkin disease (HD; n = 33) were interrogated for antibody reactivity to synthetic peptides corresponding to regions of α-syn and LMP1 containing the mimicry domain.</p></sec><sec><title>Results:</title><p>CS1-4 showed strong reactivity to wild-type human α-syn, but not to the mutant peptides or rodent α-syn. Control EBV− and EBV+ sera showed no reactivity to α-syn or LMP1 peptides. However, a significant proportion of IM and HD sera contained immunoglobulin M (IgM) (59% and 70%, in IM and HD, respectively), immunoglobulin G (IgG) (40% and 48%), and immunoglobulin A (IgA) (28% and 36%) antibodies to both peptides, as well as a significant correlation in the titers of IgM (ρ = 0.606 and 0.664, for IM and HD, respectively), IgG (0.526 and 0.836), and IgA (0.569 and 0.728) antibodies targeting LMP1 and α-syn peptides.</p></sec><sec><title>Conclusions:</title><p>Anti-EBV-LMP1 antibodies cross-reacting with a defined epitope in α-syn are present in human patients. 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uniqKey="Braak H">H Braak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woulfe, Jm" uniqKey="Woulfe J">JM Woulfe</name></author><author><name sortKey="Duke, R" uniqKey="Duke R">R Duke</name></author><author><name sortKey="Middeldorp, Jm" uniqKey="Middeldorp J">JM Middeldorp</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Ganesh, Munisha S" sort="Ganesh, Munisha S" uniqKey="Ganesh M" first="Munisha S." last="Ganesh">Munisha S. Ganesh</name><name sortKey="Gray, Madison T" sort="Gray, Madison T" uniqKey="Gray M" first="Madison T." last="Gray">Madison T. Gray</name><name sortKey="Middeldorp, Jaap M" sort="Middeldorp, Jaap M" uniqKey="Middeldorp J" first="Jaap M." last="Middeldorp">Jaap M. Middeldorp</name><name sortKey="Woulfe, John" sort="Woulfe, John" uniqKey="Woulfe J" first="John" last="Woulfe">John Woulfe</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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