DEK in the synovium of patients with juvenile idiopathic arthritis: Characterization of DEK antibodies and posttranslational modification of the DEK autoantigen
dc.contributor.author | Mor-Vaknin, Nirit | en_US |
dc.contributor.author | Kappes, Ferdinand | en_US |
dc.contributor.author | Dick, Amalie E. | en_US |
dc.contributor.author | Legendre, Maureen | en_US |
dc.contributor.author | Damoc, Catalina | en_US |
dc.contributor.author | Teitz-Tennenbaum, Seagal | en_US |
dc.contributor.author | Kwok, Roland | en_US |
dc.contributor.author | Ferrando-May, Elisa | en_US |
dc.contributor.author | Adams, Barbara S. | en_US |
dc.contributor.author | Markovitz, David M. | en_US |
dc.date.accessioned | 2011-03-10T16:03:07Z | |
dc.date.accessioned | 2011-03-10T16:03:07Z | |
dc.date.available | 2012-04-03T21:46:58Z | en_US |
dc.date.issued | 2011-02 | en_US |
dc.identifier.citation | Mor-Vaknin, Nirit; Kappes, Ferdinand; Dick, Amalie E.; Legendre, Maureen; Damoc, Catalina; Teitz-Tennenbaum, Seagal; Kwok, Roland; Ferrando-May, Elisa; Adams, Barbara S.; Markovitz, David M. (2011). "DEK in the synovium of patients with juvenile idiopathic arthritis: Characterization of DEK antibodies and posttranslational modification of the DEK autoantigen." Arthritis & Rheumatism 63(2): 556-567. <http://hdl.handle.net/2027.42/83189> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/83189 | |
dc.description.abstract | Objective DEK is a nuclear phosphoprotein and autoantigen in a subset of children with juvenile idiopathic arthritis (JIA). Autoantibodies to DEK are also found in a broad spectrum of disorders associated with abnormal immune activation. We previously demonstrated that DEK is secreted by macrophages, is released by apoptotic T cells, and attracts leukocytes. Since DEK has been identified in the synovial fluid (SF) of patients with JIA, this study was undertaken to investigate how DEK protein and/or autoantibodies may contribute to the pathogenesis of JIA. Methods DEK autoantibodies, immune complexes (ICs), and synovial macrophages were purified from the SF of patients with JIA. DEK autoantibodies and ICs were purified by affinity-column chromatography and analyzed by 2-dimensional gel electrophoresis, immunoblotting, and enzyme-linked immunosorbent assay. DEK in supernatants and exosomes was purified by serial centrifugation and immunoprecipitation with magnetic beads, and posttranslational modifications of DEK were identified by nano–liquid chromatography tandem mass spectrometry (nano–LC-MS/MS). Results DEK autoantibodies and protein were found in the SF of patients with JIA. Secretion of DEK by synovial macrophages was observed both in a free form and via exosomes. DEK autoantibodies (IgG2) may activate the complement cascade, primarily recognize the C-terminal portion of DEK protein, and exhibit higher affinity for acetylated DEK. Consistent with these observations, DEK underwent acetylation on an unprecedented number of lysine residues, as demonstrated by nano–LC-MS/MS. Conclusion These results indicate that DEK can contribute directly to joint inflammation in JIA by generating ICs through high-affinity interaction between DEK and DEK autoantibodies, a process enhanced by acetylation of DEK in the inflamed joint. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | DEK in the synovium of patients with juvenile idiopathic arthritis: Characterization of DEK antibodies and posttranslational modification of the DEK autoantigen | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor ; Drs. Mor-Vaknin, Adams, and Markovitz are coinventors on a patent pending, issued by the University of Michigan, for the use of secreted DEK as a therapeutic target. ; University of Michigan, 5240 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5640 | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationother | University of Konstanz, Konstanz, Germany | en_US |
dc.contributor.affiliationother | University of California at Davis | en_US |
dc.contributor.affiliationother | University of Konstanz, Konstanz, Germany | en_US |
dc.identifier.pmid | 21280010 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/83189/1/30138_ftp.pdf | |
dc.identifier.doi | 10.1002/art.30138 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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