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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

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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Prüfsumme: MD5:97402ff5174a88d995732be8c00d14d6

MOR-VAKNIN, Nirit, Ferdinand KAPPES, Amalie E. DICK, Maureen LEGENDRE, Catalina DAMOC, Seagal TEITZ-TENNENBAUM, Roland KWOK, Elisa FERRANDO-MAY, Barbara S. ADAMS, David M. MARKOVITZ, 2011. DEK in the synovium of patients With juvenile idiopathic arthritis characterization of DEK antibodies and posttranslational modification of the DEK autoantigen. In: Arthritis & Rheumatism. 63(2), pp. 556-567. ISSN 0004-3591. eISSN 1529-0131

@article{Mor-Vaknin2011-02synov-18239, title={DEK in the synovium of patients With juvenile idiopathic arthritis characterization of DEK antibodies and posttranslational modification of the DEK autoantigen}, year={2011}, doi={10.1002/art.30138}, number={2}, volume={63}, issn={0004-3591}, journal={Arthritis & Rheumatism}, pages={556--567}, author={Mor-Vaknin, Nirit and Kappes, Ferdinand and Dick, Amalie E. and Legendre, Maureen and Damoc, Catalina and Teitz-Tennenbaum, Seagal and Kwok, Roland and Ferrando-May, Elisa and Adams, Barbara S. and Markovitz, David M.} }

Teitz-Tennenbaum, Seagal Mor-Vaknin, Nirit Kappes, Ferdinand Adams, Barbara S. Kwok, Roland Dick, Amalie E. 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.<br />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).<br />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.<br />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. Damoc, Catalina Ferrando-May, Elisa Markovitz, David M. DEK in the synovium of patients With juvenile idiopathic arthritis characterization of DEK antibodies and posttranslational modification of the DEK autoantigen Legendre, Maureen Kwok, Roland Damoc, Catalina Adams, Barbara S. Mor-Vaknin, Nirit First publ. in: Arthritis & Rheumatism ; 63 (2011), 2. - pp. 556–567 Ferrando-May, Elisa 2011-02 eng 2013-01-31T23:25:04Z Markovitz, David M. Legendre, Maureen Kappes, Ferdinand deposit-license Teitz-Tennenbaum, Seagal 2012-03-13T07:39:15Z Dick, Amalie E.

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