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Article: Anti-dsDNA antibodies bind to mesangial annexin II in lupus nephritis

TitleAnti-dsDNA antibodies bind to mesangial annexin II in lupus nephritis
Authors
Issue Date2010
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal Of The American Society Of Nephrology, 2010, v. 21 n. 11, p. 1912-1927 How to Cite?
AbstractProduction of anti-dsDNA antibodies is a hallmark of lupus nephritis, but how these antibodies deposit in organs and elicit inflammatory damage remains unknown. In this study, we sought to identify antigens on the surface of human mesangial cells (HMC) that mediate the binding of human anti-dsDNA antibodies and the subsequent pathogenic processes. We isolated anti-dsDNA antibodies from patients with lupus nephritis by affinity chromatography. We used multiple methods to identify and characterize antigens from the plasma membrane fraction of mesangial cells that crossreacted with the anti-dsDNA antibodies. We found that annexin II mediated the binding of anti-dsDNA antibodies to HMC. After binding to the mesangial cell surface, anti-dsDNA antibodies were internalized into the cytoplasm and nucleus. This also led to induction of IL-6 secretion and annexin II synthesis, mediated through activation of p38 MAPK, JNK, and AKT. Binding of anti-dsDNA antibodies to annexin II correlated with disease activity in human lupus nephritis. Glomerular expression of annexin II correlated with the severity of nephritis, and annexin II colocalized with IgG and C3 deposits in both human and murine lupus nephritis. Gene silencing of annexin II in HMC reduced binding of anti-dsDNA antibody and partially decreased IL-6 secretion. In summary, our data demonstrate that annexin II mediates the binding of anti-dsDNA antibodies to mesangial cells, contributing to the pathogenesis of lupus nephritis. This interaction provides a potential target for therapeutic intervention. Copyright © 2010 by the American Society of Nephrology.
Persistent Identifierhttp://hdl.handle.net/10722/135249
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 7374/03M
HKU 7603/09M
Committee on Research and Conference10203476
10400647
Outstanding Researcher Award10207175
University Grants Committee20730358
Wai Hung Charitable Foundation Limited
Funding Information:

This study was supported by the Hong Kong Research Grants Council General Research Fund (HKU 7374/03M and HKU 7603/09M), Committee on Research and Conference Grants (10203476 and 10400647), an Outstanding Researcher Award (10207175), and a University Grants Committee Matching Grant Scheme (Phase III, 20730358) Dr S Yung is supported by the Endowment Fund established for the Yu Professorship in Nephrology awarded to Tak Mao Chan and the Wai Hung Charitable Foundation Limited

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorYung, Sen_HK
dc.contributor.authorCheung, KFen_HK
dc.contributor.authorZhang, Qen_HK
dc.contributor.authorChan, TMen_HK
dc.date.accessioned2011-07-27T01:30:32Z-
dc.date.available2011-07-27T01:30:32Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of The American Society Of Nephrology, 2010, v. 21 n. 11, p. 1912-1927en_HK
dc.identifier.issn1046-6673en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135249-
dc.description.abstractProduction of anti-dsDNA antibodies is a hallmark of lupus nephritis, but how these antibodies deposit in organs and elicit inflammatory damage remains unknown. In this study, we sought to identify antigens on the surface of human mesangial cells (HMC) that mediate the binding of human anti-dsDNA antibodies and the subsequent pathogenic processes. We isolated anti-dsDNA antibodies from patients with lupus nephritis by affinity chromatography. We used multiple methods to identify and characterize antigens from the plasma membrane fraction of mesangial cells that crossreacted with the anti-dsDNA antibodies. We found that annexin II mediated the binding of anti-dsDNA antibodies to HMC. After binding to the mesangial cell surface, anti-dsDNA antibodies were internalized into the cytoplasm and nucleus. This also led to induction of IL-6 secretion and annexin II synthesis, mediated through activation of p38 MAPK, JNK, and AKT. Binding of anti-dsDNA antibodies to annexin II correlated with disease activity in human lupus nephritis. Glomerular expression of annexin II correlated with the severity of nephritis, and annexin II colocalized with IgG and C3 deposits in both human and murine lupus nephritis. Gene silencing of annexin II in HMC reduced binding of anti-dsDNA antibody and partially decreased IL-6 secretion. In summary, our data demonstrate that annexin II mediates the binding of anti-dsDNA antibodies to mesangial cells, contributing to the pathogenesis of lupus nephritis. This interaction provides a potential target for therapeutic intervention. Copyright © 2010 by the American Society of Nephrology.en_HK
dc.languageengen_US
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.orgen_HK
dc.relation.ispartofJournal of the American Society of Nephrologyen_HK
dc.subject.meshAnnexin A2 - genetics - metabolism-
dc.subject.meshAntibodies, Anti-Idiotypic - metabolism-
dc.subject.meshDNA - immunology-
dc.subject.meshLupus Nephritis - metabolism - pathology-
dc.subject.meshMesangial Cells - metabolism - pathology-
dc.titleAnti-dsDNA antibodies bind to mesangial annexin II in lupus nephritisen_HK
dc.typeArticleen_HK
dc.identifier.emailYung, S:ssyyung@hku.hken_HK
dc.identifier.emailChan, TM:dtmchan@hku.hken_HK
dc.identifier.authorityYung, S=rp00455en_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1681/ASN.2009080805en_HK
dc.identifier.pmid20847146-
dc.identifier.pmcidPMC3014006-
dc.identifier.scopuseid_2-s2.0-78149305875en_HK
dc.identifier.hkuros188579en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78149305875&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue11en_HK
dc.identifier.spage1912en_HK
dc.identifier.epage1927en_HK
dc.identifier.eissn1533-3450-
dc.identifier.isiWOS:000284969500016-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10005818957-
dc.relation.projectInternalization of anti-DNA antibodies from patients with lupus nephritis by human mesangial cells-
dc.identifier.scopusauthoridYung, S=22636568800en_HK
dc.identifier.scopusauthoridCheung, KF=8763216400en_HK
dc.identifier.scopusauthoridZhang, Q=37021921200en_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK

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