Skip to main content
SpringerLink
Log in

A New Epigenetic Challenge: Systemic Lupus Erythematosus

  • Chapter
Epigenetic Contributions in Autoimmune Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 711))

Abstract

In recent years, compelling evidence has been gathered that supports a role for epigenetic alterations in the pathogenesis of systemic lupus erythematosus (SLE). Different blood cell populations of SLE patients are characterized by a global loss of DNA methylation. This process is associated with defects in ERK pathway signalling and consequent DNMT1 downregulation. Hypomethylation of gene promoters has been described, which permits transcriptional activation and therefore functional changes in the cells and also hypomethylation of the ribosomal RNA gene cluster. Among the identified targets undergoing demethylation are genes involved in autoreactivity (ITGAL), osmotic lysis and apoptosis (PRF1, MMP14 and LCN2), antigen presentation (CSF3R), inflammation (MMP14), B-T-cell interaction (CD70 and CD40LG) and cytokine pathways (CSF3R, IL-4, IL-6 and IFNGR2). DNA methylation inhibitors are also known to induce autoreactivity in vitro and cause a lupus-like disease in vivo. Further, altered patterns of histone modifications have been described in SLE. CD4+ lymphocytes undergo global histone H3 and H4 deacetylation and consequent skewed gene expression. Although multiple lines of evidence highlight the contribution of epigenetic alterations to the pathogenesis of lupus in genetically predisposed individuals, many questions remain to be answered. Attaining a deeper understanding of these matters will create opportunities in the promising area of epigenetic treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. D’Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus Lancet, 2007; 369(9561):587–596.

    Article  PubMed  Google Scholar 

  2. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med 2008; 358(9):929–939.

    Article  PubMed  CAS  Google Scholar 

  3. choper GS, Dooley MA, Treadwell EL et al. Hormonal and reproductive risk factors for development of systemic lupus erythematosus: results of a population-based, case-control study. Arthritis Rheum 2002; 46(7):1830–1839.

    Article  CAS  Google Scholar 

  4. Johnson AE, Gordon C, Palmer RG et al. The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis Rheum; 1995; 38(4):551–558.

    Article  PubMed  CAS  Google Scholar 

  5. Urowitz MB, Bookman AA, Koehler BE et al. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 1976; 60(2):221–225.

    Article  PubMed  CAS  Google Scholar 

  6. Rothfield N, Sontheimer RD, Bernstein M. Lupus erythematosus: systemic and cutaneous manifestations. Clin Dermatol 2006; 24(5):348–362.

    Article  PubMed  Google Scholar 

  7. Munoz LE, Gaipl US, Franz S, et al. SLE—a disease of clearance deficiency? Rheumatology (Oxford) 2005; 44(9):1101–1107.

    Article  CAS  Google Scholar 

  8. Baumann I, Kolowos W, Voll RE et al. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 2002; 46(1):191–201.

    Article  PubMed  Google Scholar 

  9. Isenberg DA, Manson JJ, Ehrenstein MR, et al. Fifty years of anti-ds DNA antibodies: are we approaching journey’s end? Rheumatology (Oxford) 2007; 46(7):1052–1056.

    Article  CAS  Google Scholar 

  10. Ng KP, Manson JJ, Rahman A et al. Association of antinucleosome antibodies with disease flare in serologically active clinically quiescent patients with systemic lupus erythematosus. Arthritis Rheum 2006; 55(6):900–904.

    Article  PubMed  CAS  Google Scholar 

  11. Avrameas S. Natural autoantibodies: from ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today 1991; 12(5):154–159.

    PubMed  CAS  Google Scholar 

  12. Fujii Y, Fujii K, Tanaka Y. Attempt to correct abnormal signal transduction in T-lymphocytes from systemic lupus erythematosus patients. Autoimmun Rev 2006; 5(2):143–144.

    Article  PubMed  CAS  Google Scholar 

  13. Graham RR, Kozyrev SV, Baechler EC et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 2006; 38(5):550–555.

    Article  PubMed  CAS  Google Scholar 

  14. Houssiau FA, Lefebvre C, Vanden Berghe M et al. Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity. Lupus 1995; 4(5):393–395.

    Article  PubMed  CAS  Google Scholar 

  15. Sullivan KE. Genetics of systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am 2000; 26(2):229–256, v–vi.

    Article  PubMed  CAS  Google Scholar 

  16. Rhodes B, Vyse TJ. The genetics of SLE: an update in the light of genome-wide association studies. Rheumatology (Oxford) 2008; 47(11):1603–1611.

    Article  CAS  Google Scholar 

  17. Moser KL, Kelly JA, Lessard CJ et al. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun 2009; 10(5):373–379.

    Article  PubMed  CAS  Google Scholar 

  18. Jacobson DL, Gange SJ, Rose NR et al. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 1997; 84(3):223–243.

    Article  PubMed  CAS  Google Scholar 

  19. Sanchez-Guerrero J, Karlson EW, Liang MH et al. Past use of oral contraceptives and the risk of developing systemic lupus erythematosus. Arthritis Rheum 1997; 40(5):804–808.

    Article  PubMed  CAS  Google Scholar 

  20. Mok CC, Lau CS, Ho CT et al. Do flares of systemic lupus erythematosus decline after menopause? Scand J Rheumatol 1999; 28(6):357–362.

    Article  PubMed  CAS  Google Scholar 

  21. Lahita RG, Bradlow HL, Ginzler E, etal. Low plasma androgens in women with systemic lupus erythematosus. Arthritis Rheum 1987; 30(3):241–248.

    Article  PubMed  CAS  Google Scholar 

  22. Lahita RG, Bradlow L, Fishman J et al. Estrogen metabolism in systemic lupus erythematosus: patients and family members. Arthritis Rheum 1982; 25(7):843–846.

    Article  PubMed  CAS  Google Scholar 

  23. Folomeev M, Dougados M, Beaune J et al. Plasma sex hormones and aromatase activity in tissues of patients with systemic lupus erythematosus. Lupus 1992; 1(3):191–195.

    Article  PubMed  CAS  Google Scholar 

  24. Jara LJ, Lavalle C, Espinoza LR. Does prolactin have a role in the pathogenesis of systemic lupus erythematosus? J Rheumatol 1992; 19(9):1333–1336.

    PubMed  CAS  Google Scholar 

  25. Roubinian JR, Talal N, Greenspan JS et al. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies and glomerulonephritis in NZB/NZW F1 mice. J Exp Med 1978; 147(6):1568–1583.

    Article  PubMed  CAS  Google Scholar 

  26. Roubinian JR, Papoian R, Talal N. Androgenic hormones modulate autoantibody responses and improve survival in murine lupus. J Clin Invest 1977; 59(6):1066–1070.

    Article  PubMed  CAS  Google Scholar 

  27. Elbourne KB, Keisler D, McMurray RW. Differential effects of estrogen and prolactin on autoimmune disease in the NZB/NZW F1 mouse model of systemic lupus erythematosus. Lupus 1998; 7(6):420–427.

    Article  PubMed  CAS  Google Scholar 

  28. Kremer Hovinga IC, Koopmans M, de Heer E et al. Chimerism in systemic lupus erythematosus—three hypotheses. Rheumatology (Oxford) 2007; 46(2):200–208.

    Article  CAS  Google Scholar 

  29. James JA, Harley JB, Scofield RH. Epstein-Barr virus and systemic lupus erythematosus. Curr Opin Rheumatol 2006; 18(5):462–467.

    Article  PubMed  Google Scholar 

  30. Gross AJ, Hochberg D, Rand WM et al. EBV and systemic lupus erythematosus: a new perspective. J Immunol 2005; 174(11):6599–6607.

    PubMed  CAS  Google Scholar 

  31. Sundar K, Jacques S, Gottlieb P et al. Expression of the Epstein-Barr virus nuclear antigen-1 (EBNA-1) in the mouse can elicit the production of anti-dsDNA and anti-Sm antibodies. J Autoimmun 2004; 23(2):127–140.

    Article  PubMed  CAS  Google Scholar 

  32. Poole BD, Scofield RH, Harley JB et al. Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus. Autoimmunity 2006; 39(1):63–70.

    Article  PubMed  CAS  Google Scholar 

  33. Kaufman KM, Kirby MY, Harley JB et al. Peptide mimics of a major lupus epitope of SmB/B′. Ann N Y Acad Sci 2003; 987:215–229.

    Article  PubMed  CAS  Google Scholar 

  34. Balada E, Ordi-Ros J, Vilardell-Tarres M. Molecular mechanisms mediated by human endogenous retroviruses (HERVs) in autoimmunity. Rev Med Virol 2009; 19(5):273–286.

    Article  PubMed  CAS  Google Scholar 

  35. Chu JL, Drappa J, Parnassa A et al. The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn. J Exp Med 1993; 178(2):723–730.

    Article  PubMed  CAS  Google Scholar 

  36. choper GS, Parks CG, Treadwell EL et al. Occupational risk factors for the development of systemic lupus erythematosus. J Rheumatol 2004; 31(10):1928–1933.

    Google Scholar 

  37. Portela A, Esteller M. Epigenetic modifications and their relevance to disease Nat Biotech, 2010.

    Google Scholar 

  38. Strickland FM, Richardson BC. Epigenetics in human autoimmunity. Epigenetics in autoimmunity—DNA methylation in systemic lupus erythematosus and beyond. Autoimmunity 2008; 41(4):278–286.

    Article  PubMed  CAS  Google Scholar 

  39. Rao T, Richardson B. Environmentally induced autoimmune diseases: potential mechanisms. Environ Health Perspect 1999; 107Suppl 5:737–742.

    Article  PubMed  Google Scholar 

  40. Jarvinen P, Aho K. Twin studies in rheumatic diseases. Semin Arthritis Rheum 1994; 24(1):19–28.

    Article  PubMed  CAS  Google Scholar 

  41. Singal R, Ginder GD. DNA methylation. Blood 1999; 93(12):4059–4070.

    PubMed  CAS  Google Scholar 

  42. Lister R, Pelizzola M, Dowen RH et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009; 462(7271):315–322.

    Article  PubMed  CAS  Google Scholar 

  43. Bird A. Molecular biology. Methylation talk between histones and DNA. Science 2001; 294(5549):2113–2115.

    Article  PubMed  CAS  Google Scholar 

  44. Cedar H. DNA methylation and gene activity. Cell 1988; 53(1):3–4.

    Article  PubMed  CAS  Google Scholar 

  45. Ehrlich M, Gama-Sosa MA, Huang LH et al. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 1982; 10(8):2709–2721.

    Article  PubMed  CAS  Google Scholar 

  46. Tuck-Muller CM, Narayan A, Tsien F et al. DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients. Cytogenet Cell Genet 2000; 89(1–2):121–128.

    Article  PubMed  CAS  Google Scholar 

  47. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 2006; 31(2):89–97.

    Article  PubMed  CAS  Google Scholar 

  48. Rai K, Huggins IJ, James SR et al. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase and gadd45. Cell 2008; 135(7):1201–1212.

    Article  PubMed  CAS  Google Scholar 

  49. Richardson B. Effect of an inhibitor of DNA methylation on T-cells. II. 5-Azacytidine induces self-reactivity in antigen-specific T4+ cells. Hum Immunol 1986; 17(4):456–4570.

    Article  PubMed  CAS  Google Scholar 

  50. Yung R, Powers D, Johnson K et al. Mechanisms of drug-induced lupus. II. T-cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice. J Clin Invest 1996; 97(12):2866–2871.

    Article  PubMed  CAS  Google Scholar 

  51. Richardson BC, Strahler JR, Pivirotto TS et al. Phenotypic and functional similarities between 5-azacytidine-treated T-cells and a T-cell subset in patients with active systemic lupus erythematosus. Arthritis Rheum 1992; 35(6):647–662.

    Article  PubMed  CAS  Google Scholar 

  52. Cornacchia E, Golbus J, Maybaum J et al. Hydralazine and procainamide inhibit T-cell DNA methylation and induce autoreactivity. J Immunol 1988; 140(7):2197–2200.

    PubMed  CAS  Google Scholar 

  53. Quddus J, Johnson KJ, Gavalchin J et al. Treating activated CD4+ T-cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J Clin Invest 1993; 92(1):38–53.

    Article  PubMed  CAS  Google Scholar 

  54. Yung R, Chang S, Hemati N et al. Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo. Arthritis Rheum 1997; 40(8):1436–1443.

    Article  PubMed  CAS  Google Scholar 

  55. Salvador JM, Hollander MC, Nguyen AT et al. Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity 2002; 16(4):499–508.

    Article  PubMed  CAS  Google Scholar 

  56. Emlen W, Niebur J, Kadera R. Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol 1994; 152(7):3685–3692.

    PubMed  CAS  Google Scholar 

  57. Kaplan MJ, Lewis EE, Shelden EA et al. The apoptotic ligands TRAIL, TWEAK and Fas ligand mediate monocyte death induced by autologous lupus T-cells. J Immunol 2002 169(10):6020–6029.

    PubMed  CAS  Google Scholar 

  58. Yu D, Zhu FG, Bhagat L et al. Potent CpG oligonucleotides containing phosphodiester linkages: in vitro and in vivo immunostimulatory properties. Biochem Biophys Res Commun 2002; 297(1):83–90.

    Article  PubMed  CAS  Google Scholar 

  59. Messina JP, Gilkeson GS, Pisetsky DS. The influence of DNA structure on the in vitro stimulation of murine lymphocytes by natural and synthetic polynucleotide antigens. Cell Immunol 1993; 147(1):148–157.

    Article  PubMed  CAS  Google Scholar 

  60. Wen ZK, Xu W, Xu L et al. DNA hypomethylation is crucial for apoptotic DNA to induce systemic lupus erythematosus-like autoimmune disease in SLE-nonsusceptible mice. Rheumatology (Oxford) 2007; 46(12):1796–1803.

    Article  CAS  Google Scholar 

  61. Krieg AM. CpG DNA: a pathogenic factor in systemic lupus erythematosus? J Clin Immunol 1995; 15(6):284–292.

    Article  PubMed  CAS  Google Scholar 

  62. Yung RL, Quddus J, Chrisp CE et al. Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J Immunol 1995; 154(6):3025–3035.

    PubMed  CAS  Google Scholar 

  63. Golbus J, Palella TD, Richardson BC. Quantitative changes in T-cell DNA methylation occur during differentiation and ageing. Eur J Immunol 1990; 20(8):1869–1872.

    Article  PubMed  CAS  Google Scholar 

  64. Zhang Z, Deng C, Lu Q et al. Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter. Mech Ageing Dev 2002; 123(9):1257–1268.

    Article  PubMed  CAS  Google Scholar 

  65. Richardson B, Scheinbart L, Strahler J et al. Evidence for impaired T-cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 1990; 33(11):1665–1673.

    Article  PubMed  CAS  Google Scholar 

  66. Luo Y, Li Y, Su Y et al. Abnormal DNA methylation in T-cells from patients with subacute cutaneous lupus erythematosus. Br J Dermatol 2008; 159(4):827–833.

    Article  PubMed  CAS  Google Scholar 

  67. Javierre BM, Fernandez AF, Richter J et al. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 2010; 20(2):170–179.

    Article  PubMed  CAS  Google Scholar 

  68. Lei W, Luo Y, Lei W et al. Abnormal DNA methylation in CD4+ T-cells from patients with systemic lupus erythematosus, systemic sclerosis and dermatomyositis. Scand J Rheumatol 2009;1–6.

    Google Scholar 

  69. Okada M, Ogasawara H, Kaneko H et al. Role of DNA methylation in transcription of human endogenous retrovirus in the pathogenesis of systemic lupus erythematosus. J Rheumatol 2002; 29(8):1678–1682.

    PubMed  CAS  Google Scholar 

  70. Knight SJ, Flannery AV, Hirst MC et al. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell 1993; 74(1):127–134.

    Article  PubMed  CAS  Google Scholar 

  71. Sekigawa I, Okada M, Ogasawara H et al. Lessons from similarities between SLE and HIV infection. J Infect 2002; 44(2):67–72.

    Article  PubMed  CAS  Google Scholar 

  72. Sekigawa I, Ogasawara H, Kaneko H et al. Retroviruses and autoimmunity. Intern Med 2001; 40(2):80–86.

    Article  PubMed  CAS  Google Scholar 

  73. Naito T, Ogasawara H, Kaneko H et al. Immune abnormalities induced by human endogenous retroviral peptides: with reference to the pathogenesis of systemic lupus erythematosus. J Clin Immunol 2003; 23(5):371–376.

    Article  PubMed  CAS  Google Scholar 

  74. Deng C, Kaplan MJ, Yang J et al. Decreased Ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T-lymphocytes from lupus patients. Arthritis Rheum 2001; 44(2):397–407.

    Article  PubMed  CAS  Google Scholar 

  75. Ogasawara H, Okada M, Kaneko H et al. Possible role of DNA hypomethylation in the induction of SLE: relationship to the transcription of human endogenous retroviruses. Clin Exp Rheumatol 2003; 21(6):733–738.

    PubMed  CAS  Google Scholar 

  76. Kammer GM, Perl A, Richardson BC et al. Abnormal T-cell signal transduction in systemic lupus erythematosus. Arthritis Rheum 2002; 46(5):1139–1154.

    Article  PubMed  CAS  Google Scholar 

  77. Miyamoto A, Nakayama K, Imaki H et al. Increased proliferation of B-cells and auto-immunity in mice lacking protein kinase Cdelta. Nature 2002; 416(6883):865–869.

    Article  PubMed  CAS  Google Scholar 

  78. Balada E, Ordi-Ros J, Vilardell-Tarres M. DNA methylation and systemic upus erythematosus. Ann N Y Acad Sci 2007; 1108:127–136.

    Article  PubMed  CAS  Google Scholar 

  79. Wu J, Zhou T, He J et al. Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene. J Exp Med 1993; 178(2):461–468.

    Article  PubMed  CAS  Google Scholar 

  80. Mizugaki M, Yamaguchi T, Ishiwata S et al. Alteration of DNA methylation levels in MRL lupus mice. Clin Exp Immunol 1997; 110(2):265–269.

    Article  PubMed  CAS  Google Scholar 

  81. Sawalha AH, Jeffries M. Defective DNA methylation and CD70 overexpression in CD4+ T-cells in MRL/lpr lupus-prone mice. Eur J Immunol 2007; 37(5):1407–1413.

    Article  PubMed  CAS  Google Scholar 

  82. Yoshida H, Yoshida M, Merino R et al. 5-Azacytidine inhibits the lpr gene-induced lymphadenopathy and acceleration of lupus-like syndrome in MRL/MpJ-lpr/lpr mice. Eur J Immunol 1990; 20(9):1989–1993.

    Article  PubMed  CAS  Google Scholar 

  83. Schauenstein K, Csordas A, Krömer G et al. In-vivo treatment with 5-azacytidine causes degeneration of central lymphatic organs and induces autoimmune disease in the chicken. Int J Exp Pathol 1991; 72(3):311–318.

    PubMed  CAS  Google Scholar 

  84. Guil S, Esteller M. DNA methylomes, histone codes and miRNAs: tying it all together. Int J Biochem Cell Biol 2009; 41(1):87–95.

    Article  PubMed  CAS  Google Scholar 

  85. Huang S, Rothblum LI, Chen D. Ribosomal chromatin organization. Biochem Cell Biol 2006; 84(4):444–449.

    Article  PubMed  CAS  Google Scholar 

  86. Lu Q, Kaplan M, Ray D et al. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Arthritis Rheum 2002; 46(5):1282–1291.

    Article  PubMed  CAS  Google Scholar 

  87. Hogg N, Laschinger M, Giles K et al. T-cell integrins: more than just sticking points. J Cell Sci 2003; 116(Pt 23):4695–4705.

    Article  PubMed  CAS  Google Scholar 

  88. Richardson B, Powers D, Hooper F et al. Lymphocyte function-associated antigen 1 overexpression and T-cell autoreactivity. Arthritis Rheum 1994; 37(9):1363–1372.

    Article  PubMed  CAS  Google Scholar 

  89. Robillard N, Pellat-Deceunynck C, Bataille R. Phenotypic characterization of the human myeloma cell growth fraction. Blood 2005; 105(12):4845–4848.

    Article  PubMed  CAS  Google Scholar 

  90. Puig-Kroger A, Sanchez-Elsner T, Ruiz N et al. RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements. Blood 2003; 102(9):3252–3261.

    Article  PubMed  CAS  Google Scholar 

  91. Kaplan MJ, Lu Q, Wu A et al. Demethylation of promoter regulatory elements contributes to perforin overexpression in CD4+ lupus T-cells. J Immunol 2004; 172(6):3652–3661.

    PubMed  CAS  Google Scholar 

  92. van den Broek MF, Hengartner H. The role of perforin in infections and tumour surveillance. Exp Physiol 2000; 85(6):681–685.

    Article  PubMed  Google Scholar 

  93. Kobata T, Jacquot S, Kozlowski S et al. CD27–CD70 interactions regulate B-cell activation by T-cells. Proc Natl Acad Sci USA 1995; 92(24):11249–11253.

    Article  PubMed  CAS  Google Scholar 

  94. Luo Y, Zhang X, Zhao M et al. DNA demethylation of the perforin promoter in CD4(+) T-cells from patients with subacute cutaneous lupus erythematosus. J Dermatol Sci 2009; 56(1):33–36.

    Article  PubMed  CAS  Google Scholar 

  95. Oelke K, Lu Q, Richardson D et al. Overexpression of CD70 and overstimulation of IgG synthesis by lupus T-cells and T-cells treated with DNA methylation inhibitors. Arthritis Rheum 2004; 50(6):1850–1860.

    Article  PubMed  CAS  Google Scholar 

  96. Luo Y, Zhao M, Lu Q. Demethylation of promoter regulatory elements contributes to CD70 overexpression in CD4+ T-cells from patients with subacute cutaneous lupus erythematosus. Clin Exp Dermatol 2009.

    Google Scholar 

  97. Lu Q, Wu A, Richardson BC. Demethylation of the same promoter sequence increases CD70 expression in lupus T-cells and T-cells treated with lupus-inducing drugs. J Immunol 2005; 174(10):6212–6219.

    PubMed  CAS  Google Scholar 

  98. Lu Q, Wu A, Tesmer L et al. Demethylation of CD40LG on the inactive X in T-cells from women with lupus. J Immunol 2007; 179(9):6352–6358.

    PubMed  CAS  Google Scholar 

  99. Zhou Y, Yuan J, Pan Y et al. T-cell CD40LG gene expression and the production of IgG by autologous B cells in systemic lupus erythematosus. Clin Immunol 2009; 132(3):362–370.

    Article  PubMed  CAS  Google Scholar 

  100. Mi XB, Zeng FQ. Hypomethylation of interleukin-4 and-6 promoters in T-cells from systemic lupus erythematosus patients. Acta Pharmacol Sin 2008; 29(1):105–112.

    Article  PubMed  CAS  Google Scholar 

  101. Evans JL, Boyle WJ, Ting JP. Molecular basis of elevated c-myb expression in the abnormal L3T4-, Lyt-2-T-lymphocytes of autoimmune mice. J Immunol 1987; 139(10):3497–3505.

    PubMed  CAS  Google Scholar 

  102. Eleftheriades EG, Boumpas DT, Balow JE et al. Transcriptional and posttranscriptional mechanisms are responsible for the increased expression of c-myc protooncogene in lymphocytes from patients with systemic lupus erythematosus. Clin Immunol Immunopathol 1989; 52(3):507–515.

    Article  PubMed  CAS  Google Scholar 

  103. Strahl BD, Allis CD. The language of covalent histone modifications. Nature 2000; 403(6765):41–45.

    Article  PubMed  CAS  Google Scholar 

  104. Peterson CL, Laniel MA.Histones and histone modifications. Curr Biol 2004;14(14):R546–R551.

    Article  PubMed  CAS  Google Scholar 

  105. Santos-Rosa H, Caldas C. Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 2005; 41(16):2381–2402.

    Article  PubMed  CAS  Google Scholar 

  106. Matouk CC, Marsden PA. Epigenetic regulation of vascular endothelial gene expression. Circ Res 2008; 102(8):873–887.

    Article  PubMed  CAS  Google Scholar 

  107. Boix-Chornet M, Fraga MF, Villar-Garea A et al. Release of hypoacetylated and trimethylated histone H4 is an epigenetic marker of early apoptosis. J Biol Chem 2006; 281(19):13540–13547.

    Article  PubMed  CAS  Google Scholar 

  108. Dieker JW, Fransen JH, van Bavel CC et al. Apoptosis-induced acetylation of histones is pathogenic in systemic lupus erythematosus. Arthritis Rheum 2007; 56(6):1921–1933.

    Article  PubMed  CAS  Google Scholar 

  109. van Bavel CC, Dieker J, Muller S et al. Apoptosis-associated acetylation on histone H2B is an epitope for lupus autoantibodies. Mol Immunol 2009; 47(2–3):511–516.

    Article  PubMed  CAS  Google Scholar 

  110. Mishra N, Reilly CM, Brown DR et al. Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse. J Clin Invest 2003; 111(4):539–552.

    PubMed  CAS  Google Scholar 

  111. Reilly CM, Mishra N, Miller JM et al. Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid. J Immunol 2004 173(6):4171–4178.

    PubMed  CAS  Google Scholar 

  112. Forster N, Gallinat S, Jablonska J et al. p300 protein acetyltransferase activity suppresses systemic lupus erythematosus-like autoimmune disease in mice. J Immunol 2007; 178(11):6941–6948.

    PubMed  CAS  Google Scholar 

  113. Garcia BA, Busby SA, Shabanowitz J et al. Resetting the epigenetic histone code in the MRL-lpr/lpr mouse model of lupus by histone deacetylase inhibition. J Proteome Res 2005; 4(6):2032–2042.

    Article  PubMed  CAS  Google Scholar 

  114. Hu N, Qiu X, Luo Y et al. Abnormal histone modification patterns in lupus CD4+ T-cells. J Rheumatol 2008; 35(5):804–810.

    PubMed  CAS  Google Scholar 

  115. Mishra N, Brown DR, Olorenshaw IM et al. Trichostatin A reverses skewed expression of CD154, interleukin-10 and interferon-gamma gene and protein expression in lupus T-cells. Proc Natl Acad Sci USA 2001; 98(5):2628–2633.

    Article  PubMed  CAS  Google Scholar 

  116. Zhang Z, Song L, Maurer K et al. Global H4 acetylation analysis by ChIP-chip in systemic lupus erythematosus monocytes. Genes Immun, 2009.

    Google Scholar 

  117. Yoo CB, Jones PA. Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 2006; 5(1):37–50.

    Article  PubMed  CAS  Google Scholar 

  118. Adcock IM. HDAC inhibitors as anti-inflammatory agents. Br J Pharmacol 2007; 150(7):829–831.

    Article  PubMed  CAS  Google Scholar 

  119. Brogdon JL, Xu Y, Szabo SJ et al. Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function. Blood 2007; 109(3):1123–1130.

    Article  PubMed  CAS  Google Scholar 

  120. Javierre BM, Esteller M, Ballestar E. Epigenetic connections between autoimmune disorders and haematological malignancies. Trends Immunol 2008; 29(12):616–623.

    Article  PubMed  CAS  Google Scholar 

  121. Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun 2009; 32(3–4):189–194.

    Article  PubMed  CAS  Google Scholar 

  122. Wang Y, Liang Y, Lu Q. MicroRNA epigenetic alterations: predicting biomarkers and therapeutic targets in human diseases. Clin Genet 2008; 74(4):307–315.

    Article  PubMed  CAS  Google Scholar 

  123. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism and function. Cell 2004; 116(2):281–297.

    Article  PubMed  CAS  Google Scholar 

  124. Lujambio A, Calin GA, Villanueva A et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA, 2008. 105(36):13556–13561.

    Article  PubMed  CAS  Google Scholar 

  125. Dai Y, Huang YS, Tang M et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 2007; 16(12):939–946.

    Article  PubMed  CAS  Google Scholar 

  126. Tang Y, Luo X, Cui H et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 2009; 60(4):1065–1075.

    Article  PubMed  CAS  Google Scholar 

  127. Sawalha AH, Harley JB. Antinuclear autoantibodies in systemic lupus erythematosus. Curr Opin Rheumatol 2004; 16(5):534–540.

    Article  PubMed  Google Scholar 

  128. Mannik M, Merrill CE, Stamps LD et al. Multiple autoantibodies form the glomerular immune deposits in patients with systemic lupus erythematosus. J Rheumatol 2003; 30(7):1495–1504.

    PubMed  Google Scholar 

  129. Amoura Z, Koutouzov S, Chabre H et al. Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases: antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus. Arthritis Rheum 2000; 43(1):76–84.

    Article  PubMed  CAS  Google Scholar 

  130. Kowal C, Degiorgio LA, Lee JY et al. Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci USA 2006; 103(52):19854–19859.

    Article  PubMed  CAS  Google Scholar 

  131. Becker-Merok A, Kalaaji M, Haugbro K et al. Alpha-actinin-binding antibodies in relation to systemic lupus erythematosus and lupus nephritis. Arthritis Res Ther 2006; 8(6):R162.

    Article  PubMed  CAS  Google Scholar 

  132. Siegert CE, Daha MR, Swaak AJ et al. The relationship between serum titers of autoantibodies to C1q and age in the general population and in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 1993; 67(3 Pt 1):204–209.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

    Biola M. Javierre

  2. Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Bruce Richardson

Authors
  1. Biola M. Javierre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruce Richardson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain

    Esteban Ballestar PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Javierre, B.M., Richardson, B. (2011). A New Epigenetic Challenge: Systemic Lupus Erythematosus. In: Ballestar, E. (eds) Epigenetic Contributions in Autoimmune Disease. Advances in Experimental Medicine and Biology, vol 711. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8216-2_9

Download citation

Publish with us

Policies and ethics

Search

Navigation