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DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen.

Publication ,  Journal Article
Mor-Vaknin, N; Kappes, F; Dick, AE; Legendre, M; Damoc, C; Teitz-Tennenbaum, S; Kwok, R; Ferrando-May, E; Adams, BS; Markovitz, DM
Published in: Arthritis and rheumatism
February 2011

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.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).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.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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Published In

Arthritis and rheumatism

DOI

EISSN

1529-0131

ISSN

0004-3591

Publication Date

February 2011

Volume

63

Issue

2

Start / End Page

556 / 567

Related Subject Headings

  • Synovial Membrane
  • Synovial Fluid
  • Protein Processing, Post-Translational
  • Poly-ADP-Ribose Binding Proteins
  • Oncogene Proteins
  • Macrophages
  • Joints
  • Humans
  • Chromosomal Proteins, Non-Histone
  • Child
 

Citation

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MLA
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Mor-Vaknin, N., Kappes, F., Dick, A. E., Legendre, M., Damoc, C., Teitz-Tennenbaum, S., … Markovitz, D. M. (2011). DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen. Arthritis and Rheumatism, 63(2), 556–567. https://doi.org/10.1002/art.30138
Mor-Vaknin, Nirit, Ferdinand Kappes, Amalie E. Dick, Maureen Legendre, Catalina Damoc, Seagal Teitz-Tennenbaum, Roland Kwok, Elisa Ferrando-May, Barbara S. Adams, and David M. Markovitz. “DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen.Arthritis and Rheumatism 63, no. 2 (February 2011): 556–67. https://doi.org/10.1002/art.30138.
Mor-Vaknin N, Kappes F, Dick AE, Legendre M, Damoc C, Teitz-Tennenbaum S, et al. DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen. Arthritis and rheumatism. 2011 Feb;63(2):556–67.
Mor-Vaknin, Nirit, et al. “DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen.Arthritis and Rheumatism, vol. 63, no. 2, Feb. 2011, pp. 556–67. Epmc, doi:10.1002/art.30138.
Mor-Vaknin N, Kappes F, Dick AE, Legendre M, Damoc C, Teitz-Tennenbaum S, Kwok R, Ferrando-May E, Adams BS, Markovitz DM. DEK in the synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen. Arthritis and rheumatism. 2011 Feb;63(2):556–567.
Journal cover image

Published In

Arthritis and rheumatism

DOI

EISSN

1529-0131

ISSN

0004-3591

Publication Date

February 2011

Volume

63

Issue

2

Start / End Page

556 / 567

Related Subject Headings

  • Synovial Membrane
  • Synovial Fluid
  • Protein Processing, Post-Translational
  • Poly-ADP-Ribose Binding Proteins
  • Oncogene Proteins
  • Macrophages
  • Joints
  • Humans
  • Chromosomal Proteins, Non-Histone
  • Child