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
  2. Alexander, (2013) Ann Rheum Dis 72: pp. 1549 f="http://dx.doi.org/10.1136/annrheumdis-2012-202216" target="_blank" title="It opens in new window">CrossRef
  3. Alexander, (2009) Blood 113: pp. 214 f="http://dx.doi.org/10.1182/blood-2008-07-168286" target="_blank" title="It opens in new window">CrossRef
  4. Altorok, (2013) Curr Opin Rheumatol 25: pp. 569 f="http://dx.doi.org/10.1097/BOR.0b013e328364206f" target="_blank" title="It opens in new window">CrossRef
  5. Ambrosi, (2014) Exp Cell Res 325: pp. 2 f="http://dx.doi.org/10.1016/j.yexcr.2014.01.003" target="_blank" title="It opens in new window">CrossRef
  6. Baechler, (2003) Proc Natl Acad Sci U S A 100: pp. 2610 f="http://dx.doi.org/10.1073/pnas.0337679100" target="_blank" title="It opens in new window">CrossRef
  7. Belot, (2012) Pediatr Rheumatol Online J 10: pp. 21 f="http://dx.doi.org/10.1186/1546-0096-10-21" target="_blank" title="It opens in new window">CrossRef
  8. Blanco, (2001) Science 294: pp. 1540 f="http://dx.doi.org/10.1126/science.1064890" target="_blank" title="It opens in new window">CrossRef
  9. Blanco, (2005) Arthritis Rheum 52: pp. 201 f="http://dx.doi.org/10.1002/art.20745" target="_blank" title="It opens in new window">CrossRef
  10. Bravo-Zehnder, (2015) Arthritis Rheum 67: pp. 204 f="http://dx.doi.org/10.1002/art.38900" target="_blank" title="It opens in new window">CrossRef
  11. Brinkmann, (2004) Science 303: pp. 1532 f="http://dx.doi.org/10.1126/science.1092385" target="_blank" title="It opens in new window">CrossRef
  12. Cheng, (2013) Ann Rheum Dis 72: pp. 2011 f="http://dx.doi.org/10.1136/annrheumdis-2013-203455" target="_blank" title="It opens in new window">CrossRef
  13. Crispin, (2008) J Immunol 181: pp. 8761 f="http://dx.doi.org/10.4049/jimmunol.181.12.8761" target="_blank" title="It opens in new window">CrossRef
  14. Crow, (2014) J Immunol 192: pp. 5459 f="http://dx.doi.org/10.4049/jimmunol.1002795" target="_blank" title="It opens in new window">CrossRef
  15. Dai, (2014) Curr Opin Immunol 31C: pp. 87 f="http://dx.doi.org/10.1016/j.coi.2014.10.004" target="_blank" title="It opens in new window">CrossRef
  16. Doria, (2002) Arthritis Rheum 47: pp. 202 f="http://dx.doi.org/10.1002/art.10248" target="_blank" title="It opens in new window">CrossRef
  17. Gall, (2012) Immunity 36: pp. 120 f="http://dx.doi.org/10.1016/j.immuni.2011.11.018" target="_blank" title="It opens in new window">CrossRef
  18. Giannakopoulos, (2013) N Engl J Med 368: pp. 1033 f="http://dx.doi.org/10.1056/NEJMra1112830" target="_blank" title="It opens in new window">CrossRef
  19. Hakkim, (2010) Proc Natl Acad Sci U S A 107: pp. 9813 f="http://dx.doi.org/10.1073/pnas.0909927107" target="_blank" title="It opens in new window">CrossRef
  20. Hiepe, (2015) Z Rheumatol 74: pp. 20 f="http://dx.doi.org/10.1007/s00393-014-1438-4" target="_blank" title="It opens in new window">CrossRef
  21. Hughes, (2011) Arthritis Res Ther 13: pp. 245 f="http://dx.doi.org/10.1186/ar3484" target="_blank" title="It opens in new window">CrossRef
  22. Humrich, (2010) Proc Natl Acad Sci U S A 107: pp. 204 f="http://dx.doi.org/10.1073/pnas.0903158107" target="_blank" title="It opens in new window">CrossRef
  23. Humrich JY, Spee-Mayer C von, Siegert E et al (2015) Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. doi:10.1136/annrheumdis-2014-206506
  24. Knight, (2012) Curr Opin Rheumatol 24: pp. 441 f="http://dx.doi.org/10.1097/BOR.0b013e3283546703" target="_blank" title="It opens in new window">CrossRef
  25. Kowal, (2006) Proc Natl Acad Sci U S A 103: pp. 19854 f="http://dx.doi.org/10.1073/pnas.0608397104" target="_blank" title="It opens in new window">CrossRef
  26. Kyogoku, (2013) PLoS One 8: pp. e83776 f="http://dx.doi.org/10.1371/journal.pone.0083776" target="_blank" title="It opens in new window">CrossRef
  27. Lech, (2013) J Am Soc Nephrol 24: pp. 1357 f="http://dx.doi.org/10.1681/ASN.2013010026" target="_blank" title="It opens in new window">CrossRef
  28. Lu-Fritts, (2014) Arthritis Rheum 66: pp. 3105 f="http://dx.doi.org/10.1002/art.38786" target="_blank" title="It opens in new window">CrossRef
  29. Munoz, (2010) Nat Rev Rheumatol 6: pp. 280 f="http://dx.doi.org/10.1038/nrrheum.2010.46" target="_blank" title="It opens in new window">CrossRef
  30. Scofield, (2008) Arthritis Rheum 58: pp. 2511 f="http://dx.doi.org/10.1002/art.23701" target="_blank" title="It opens in new window">CrossRef
  31. Smith-Bouvier, (2008) J Exp Med 205: pp. 1099 f="http://dx.doi.org/10.1084/jem.20070850" target="_blank" title="It opens in new window">CrossRef
  32. Stohl, (2012) Arthritis Rheum 64: pp. 2328 f="http://dx.doi.org/10.1002/art.34400" target="_blank" title="It opens in new window">CrossRef
  33. Stojan, (2012) Expert Rev Clin Immunol 8: pp. 439 f="http://dx.doi.org/10.1586/eci.12.36" target="_blank" title="It opens in new window">CrossRef
  34. Tsokos, (2011) N Engl J Med 365: pp. 2110 f="http://dx.doi.org/10.1056/NEJMra1100359" target="_blank" title="It opens in new window">CrossRef
  35. Wahren-Herlenius, (2013) Lancet 382: pp. 819 f="http://dx.doi.org/10.1016/S0140-6736(13)60954-X" target="_blank" title="It opens in new window">CrossRef
  36. Wang, (2002) J Immunol 168: pp. 2046 f="http://dx.doi.org/10.4049/jimmunol.168.4.2046" target="_blank" title="It opens in new window">CrossRef
  
• 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.