Display options
Cite
Podolska MJ, Biermann MH, Maueröder C, et al. Inflammatory etiopathogenesis of systemic lupus erythematosus: an update. J Inflamm Res. 2015;8:161-71doi: 10.2147/JIR.S70325.
Podolska, M. J., Biermann, M. H., Maueröder, C., Hahn, J., & Herrmann, M. (2015). Inflammatory etiopathogenesis of systemic lupus erythematosus: an update. Journal of inflammation research, 8161-71. https://doi.org/10.2147/JIR.S70325
Podolska, Malgorzata J, et al. "Inflammatory etiopathogenesis of systemic lupus erythematosus: an update." Journal of inflammation research vol. 8 (2015): 161-71. doi: https://doi.org/10.2147/JIR.S70325
Podolska MJ, Biermann MH, Maueröder C, Hahn J, Herrmann M. Inflammatory etiopathogenesis of systemic lupus erythematosus: an update. J Inflamm Res. 2015 Aug 20;8:161-71. doi: 10.2147/JIR.S70325. eCollection 2015. PMID: 26316795; PMCID: PMC4548750.
Copy Download .nbib Format: NLM
Share it on

J Inflamm Res. 2015 Aug 20;8:161-71. doi: 10.2147/JIR.S70325. eCollection 2015.

Inflammatory etiopathogenesis of systemic lupus erythematosus: an update.

Journal of inflammation research

Malgorzata J Podolska, Mona Hc Biermann, Christian Maueröder, Jonas Hahn, Martin Herrmann

Affiliations

  1. Department of Internal Medicine 3, Institute for Clinical Immunology and Rheumatology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.

PMID: 26316795 PMCID: PMC4548750 DOI: 10.2147/JIR.S70325

Abstract

The immune system struggles every day between responding to foreign antigens and tolerating self-antigens to delicately maintain tissue homeostasis. If self-tolerance is broken, the development of autoimmunity can be the consequence, as it is in the case of the chronic inflammatory autoimmune disease systemic lupus erythematosus (SLE). SLE is considered to be a multifactorial disease comprising various processes and cell types that act abnormally and in a harmful way. Oxidative stress, infections, or, in general, tissue injury are accompanied by massive cellular demise. Several processes such as apoptosis, necrosis, or NETosis (formation of Neutrophil Extracellular Traps [NETs]) may occur alone or in combination. If clearance of dead cells is insufficient, cellular debris may accumulate and trigger inflammation and leakage of cytoplasmic and nuclear autoantigens like ribonucleoproteins, DNA, or histones. Inadequate removal of cellular remnants in the germinal centers of secondary lymphoid organs may result in the presentation of autoantigens by follicular dendritic cells to autoreactive B cells that had been generated by chance during the process of somatic hypermutation (loss of peripheral tolerance). The improper exposure of nuclear autoantigens in this delicate location is consequently prone to break self-tolerance to nuclear autoantigens. Indeed, the germline variants of autoantibodies often do not show autoreactivity. The subsequent production of autoantibodies plays a critical role in the development of the complex immunological disorder fostering SLE. Immune complexes composed of cell-derived autoantigens and autoantibodies are formed and get deposited in various tissues, such as the kidney, leading to severe organ damage. Alternatively, they may also be formed in situ by binding to planted antigens of circulating autoantibodies. Here, we review current knowledge about the etiopathogenesis of SLE including the involvement of different types of cell death, serving as the potential source of autoantigens, and impaired clearance of cell remnants, causing accumulation of cellular debris.

Keywords: NETosis; apoptosis; autoimmunity; cell death; clearance deficiency; systemic lupus erythematosus

References

  1. Semin Arthritis Rheum. 2010 Feb;39(4):257-68 - PubMed
  2. Arthritis Rheum. 2001 Nov;44(11):2642-52 - PubMed
  3. Arthritis Rheum. 1997 Dec;40(12):2162-71 - PubMed
  4. Science. 2006 Aug 4;313(5787):670-3 - PubMed
  5. Lupus. 1998;7(2):113-8 - PubMed
  6. Molecules. 2009 Nov 30;14(12):4892-914 - PubMed
  7. Lupus. 2011 Mar;20(3):250-5 - PubMed
  8. Arthritis Rheum. 1998 Jul;41(7):1241-50 - PubMed
  9. J Pathol. 2011 Jan;223(2):177-94 - PubMed
  10. Blood. 2011 Jan 20;117(3):953-9 - PubMed
  11. J Immunol. 2000 Feb 1;164(3):1322-32 - PubMed
  12. J Cell Biol. 2007 Jan 15;176(2):231-41 - PubMed
  13. Arthritis Rheum. 1987 Nov;30(11):1289-92 - PubMed
  14. Ann Rheum Dis. 2001 Oct;60(10):950-5 - PubMed
  15. Autoimmunity. 2009 May;42(4):269-71 - PubMed
  16. Nat Rev Rheumatol. 2010 May;6(5):280-9 - PubMed
  17. J Immunol. 1989 Jul 1;143(1):103-12 - PubMed
  18. Eur J Immunol. 2002 Jul;32(7):1958-68 - PubMed
  19. Phys Biol. 2013 Dec;10(6):065006 - PubMed
  20. J Biol Chem. 2002 Dec 20;277(51):49562-8 - PubMed
  21. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19246-51 - PubMed
  22. Nat Rev Immunol. 2008 Apr;8(4):279-89 - PubMed
  23. Can J Gastroenterol. 2001 Mar;15(3):166-76 - PubMed
  24. Apoptosis. 2010 Sep;15(9):1007-28 - PubMed
  25. Arthritis Rheum. 2012 Apr;64(4):1247-56 - PubMed
  26. Autoimmunity. 2013 Mar;46(2):121-7 - PubMed
  27. Nat Clin Pract Rheumatol. 2006 Sep;2(9):481-90 - PubMed
  28. Environ Health Perspect. 1999 Oct;107 Suppl 5:693-700 - PubMed
  29. Blood. 2006 Dec 15;108(13):4094-101 - PubMed
  30. J Exp Med. 2009 Aug 31;206(9):1983-94 - PubMed
  31. J Biochem. 2000 Mar;127(3):411-7 - PubMed
  32. Br J Cancer. 1972 Aug;26(4):239-57 - PubMed
  33. Autoimmun Rev. 2015 Jan;14(1):43-8 - PubMed
  34. Arthritis Rheum. 1998 Sep;41(9):1663-8 - PubMed
  35. Sci Transl Med. 2011 Mar 9;3(73):73ra19 - PubMed
  36. Nature. 1997 Nov 27;390(6658):350-1 - PubMed
  37. Acta Haematol. 1997;98(1):8-13 - PubMed
  38. J Autoimmun. 2007 Mar-May;28(2-3):114-21 - PubMed
  39. Expert Rev Clin Immunol. 2014 Sep;10(9):1151-64 - PubMed
  40. Rheumatology (Oxford). 2008 Nov;47(11):1603-11 - PubMed
  41. PLoS One. 2008 Jan 09;3(1):e1413 - PubMed
  42. J Biol Chem. 2012 Jan 2;287(1):496-503 - PubMed
  43. J Exp Med. 1998 Dec 21;188(12 ):2313-20 - PubMed
  44. J Biol Chem. 1999 Sep 24;274(39):27786-92 - PubMed
  45. Eur J Immunol. 2001 Jul;31(7):1981-8 - PubMed
  46. Nature. 1998 Jan 1;391(6662):96-9 - PubMed
  47. Rheumatology (Oxford). 2005 Sep;44(9):1101-7 - PubMed
  48. Autoimmunity. 2012 Dec;45(8):588-92 - PubMed
  49. Autoimmunity. 2012 Dec;45(8):597-601 - PubMed
  50. Arthritis Rheum. 2013 Feb;65(2):447-56 - PubMed
  51. Nat Med. 2014 May;20(5):511-7 - PubMed
  52. Mol Cell Biol. 2012 Jul;32(14):2698-708 - PubMed
  53. Lab Invest. 2000 May;80(5):617-53 - PubMed
  54. Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):887-92 - PubMed
  55. Arthritis Rheum. 2012 Nov;64(11):3666-76 - PubMed
  56. Immunity. 2007 Dec;27(6):927-40 - PubMed
  57. Lupus. 2005;14(6):423-5 - PubMed
  58. Biochim Biophys Acta. 2002 Dec 30;1585(2-3):53-63 - PubMed
  59. Ann Rheum Dis. 2006 Jul;65(7):942-5 - PubMed
  60. Science. 2004 Mar 5;303(5663):1532-5 - PubMed
  61. Science. 2004 Mar 5;303(5663):1529-31 - PubMed
  62. Cell. 1997 Apr 18;89(2):175-84 - PubMed
  63. Ann Rheum Dis. 2010 Jan;69(1):20-8 - PubMed
  64. Nat Rev Rheumatol. 2012 Sep;8(9):522-33 - PubMed
  65. Cytokine Growth Factor Rev. 2008 Feb;19(1):41-52 - PubMed
  66. Front Immunol. 2012 Sep 03;3:277 - PubMed
  67. Lupus. 2015 May;24(6):569-81 - PubMed
  68. Nat Immunol. 2010 Sep;11(9):785-97 - PubMed
  69. J Intensive Care. 2013 Dec 04;1(1):13 - PubMed
  70. J Exp Med. 2007 Jan 22;204(1):11-5 - PubMed
  71. Arthritis Rheum. 2002 Jan;46(1):191-201 - PubMed
  72. Autoimmun Rev. 2010 Nov;10(1):38-42 - PubMed
  73. Front Immunol. 2012 Oct 04;3:306 - PubMed
  74. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6632-6 - PubMed
  75. Front Immunol. 2014 Nov 11;5:560 - PubMed
  76. Arthritis Rheum. 2004 Feb;50(2):640-9 - PubMed
  77. J Intern Med. 2011 Oct;270(4):309-18 - PubMed
  78. J Cell Sci. 2007 Jul 1;120(Pt 13):2143-9 - PubMed
  79. Apoptosis. 2010 Sep;15(9):1098-113 - PubMed
  80. Ann Rheum Dis. 2013 Jul;72(7):1239-48 - PubMed
  81. Nature. 1994 Sep 22;371(6495):346-7 - PubMed
  82. Ann Rheum Dis. 2011 Nov;70(11):1905-13 - PubMed
  83. Nat Rev Immunol. 2007 Dec;7(12):964-74 - PubMed
  84. J Immunol. 1991 Jul 1;147(1):117-23 - PubMed
  85. Bioessays. 2003 Nov;25(11):1106-18 - PubMed
  86. Nat Med. 1995 Mar;1(3):237-43 - PubMed
  87. Transfus Apher Sci. 2007 Apr;36(2):187-93 - PubMed
  88. Nature. 1998 Mar 19;392(6673):245-52 - PubMed
  89. Arthritis Rheum. 2009 Jun;60(6):1733-42 - PubMed
  90. Science. 1942 Nov 6;96(2497):428-30 - PubMed
  91. Arthritis Res Ther. 2010;12(2):207 - PubMed
  92. J Leukoc Biol. 1997 Apr;61(4):375-80 - PubMed
  93. Cell Mol Immunol. 2008 Feb;5(1):9-21 - PubMed
  94. J Biol Chem. 1995 Aug 11;270(32):18715-8 - PubMed
  95. Clin Rev Allergy Immunol. 2008 Jun;34(3):345-7 - PubMed
  96. J Biol Chem. 2001 Jan 12;276(2):1071-7 - PubMed
  97. Front Immunol. 2014 Apr 09;5:164 - PubMed
  98. J Cell Biol. 2010 Nov 1;191(3):677-91 - PubMed
  99. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9813-8 - PubMed
  100. Immunol Today. 1998 Nov;19(11):511-4 - PubMed
  101. Ann Rheum Dis. 2011 Dec;70(12):2071-4 - PubMed
  102. Int Rev Immunol. 2010 Apr;29(2):184-209 - PubMed
  103. Nat Med. 2008 Jul;14(7):748-55 - PubMed
  104. J Clin Invest. 2009 Jan;119(1):20-32 - PubMed
  105. EMBO J. 2001 Jun 15;20(12):3046-55 - PubMed
  106. Immunobiology. 2003;207(1):73-81 - PubMed
  107. J Assoc Physicians India. 2004 Jul;52:533-7 - PubMed
  108. J Autoimmun. 2015 Apr;58:59-66 - PubMed
  109. J Exp Med. 2008 Dec 22;205(13):3007-18 - PubMed
  110. Trends Immunol. 2006 May;27(5):244-50 - PubMed
  111. Sci Transl Med. 2011 Mar 9;3(73):73ra20 - PubMed
  112. Eur J Immunol. 1992 Jul;22(7):1719-28 - PubMed
  113. Phys Biol. 2013 Dec;10(6):065007 - PubMed
  114. Clin Immunol Immunopathol. 1995 Feb;74(2):135-42 - PubMed
  115. Expert Opin Biol Ther. 2014 Nov;14(11):1701-8 - PubMed

Publication Types