Pathogenese des systemischen Lupus erythematodes

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• 作者：T. Alexander (1)
  A. Radbruch (1)
  Prof. Dr. F. Hiepe (1)
  
  1. Medizinische Klinik m. S. Rheumatologie und Klinische Immunologie ; Charit茅 - Universit盲tsmedizin Berlin ; Deutsches RheumaForschungszentrum Berlin 鈥?ein Institut der Leibniz-Gemeinschaft ; Charit茅platz 1 ; 10117 ; Berlin ; Deutschland
  
• 关键词：Lupus ; Genetische Faktoren ; NETose ; Interferon ; B ; Zell ; Hyperaktivit盲t ; Autoantik枚rper ; Lupus erythematosus ; Genetic factors ; NETosis ; Interferon ; B cell hyperactivity ; Autoantibodies
• 刊名：Zeitschrift f篓鹿r Rheumatologie
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：74
• 期：3
• 页码：183-190
• 全文大小：551 KB
• 参考文献：1. Alexander T, Sarfert R, Klotsche J et al (2015) The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus. Ann Rheum Dis. doi:10.1136/annrheumdis-2014-206016
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• 刊物主题：Internal Medicine; Rheumatology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1435-1250

文摘

Systemic lupus erythematosus (SLE) is an autoimmune disease with an extremely complex pathogenesis. Due to a genetic predisposition the disease can be induced by multiple stress factors involving epigenetic mechanisms and under the influence of the innate immune system. Defective clearance of immune complexes and apoptotic material together with enhanced neutrophil extracellular trap formation (NETosis) as well as up-regulation of type 1 interferon in particular, drive the adaptive immune system to a breakdown of self-tolerance. The result is a B cell hyperactivity, which leads to the generation of a multitude of different autoantibodies that are not only directed against nuclear antigens. Autoantibodies are the initiators for the involvement of many organs, which enhances further inflammatory cells and cytokines by participation of effector T-cells. Finally, an autoreactive immunological (plasma cell) memory is formed, which contributes to chronification and is associated with therapy-refractive courses of the disease. The depletion of the autoreactive immunological memory by immunoablation can lead to induction of self-tolerance and long-term remission.