| DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen. | |
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MedLine Citation:
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PMID: 21280010 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Nirit Mor-Vaknin; Ferdinand Kappes; Amalie E Dick; Maureen Legendre; Catalina Damoc; Seagal Teitz-Tennenbaum; Roland Kwok; Elisa Ferrando-May; Barbara S Adams; David M Markovitz |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arthritis and rheumatism Volume: 63 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-31 Completed Date: 2011-03-08 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 556-67 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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University of Michigan, Ann Arbor, MI 48109-5640, USA. morvak@umich.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation Antigen-Antibody Complex / immunology, metabolism Arthritis, Juvenile Rheumatoid / immunology, metabolism*, pathology Autoantibodies / blood Autoantigens / immunology, metabolism* Child Chromosomal Proteins, Non-Histone / immunology, metabolism* Humans Joints / metabolism, pathology Macrophages / metabolism, pathology Oncogene Proteins / immunology, metabolism* Protein Processing, Post-Translational* Synovial Fluid / chemistry, metabolism Synovial Membrane / metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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5-P30-AR-048310-07/AR/NIAMS NIH HHS; K01 AR055620-01A2/AR/NIAMS NIH HHS; K01-AR-055620/AR/NIAMS NIH HHS; P30 AR048310-07/AR/NIAMS NIH HHS; R01 AI062248-05/AI/NIAID NIH HHS; R01 AI087128-01/AI/NIAID NIH HHS; R01 DK067102-01A3/DK/NIDDK NIH HHS; R01-AI-062248/AI/NIAID NIH HHS; R01-AI-087128/AI/NIAID NIH HHS; R01-DK-067102/DK/NIDDK NIH HHS; R03 AR056748-01/AR/NIAMS NIH HHS; R03-AR-056748-01/AR/NIAMS NIH HHS; T32 CA088784-03/CA/NCI NIH HHS; T32-CA-88784-03/CA/NCI NIH HHS; UL1 RR024986-02/RR/NCRR NIH HHS; UL1-RR-024986/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigen-Antibody Complex; 0/Autoantibodies; 0/Autoantigens; 0/Chromosomal Proteins, Non-Histone; 0/Dek protein, human; 0/Oncogene Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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