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Pathology of Systemic Lupus Erythematosus: The Challenges Ahead

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Book cover Systemic Lupus Erythematosus

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1134))

Abstract

Many studies have explored the pathology of systemic lupus erythematosus (SLE), an autoimmune rheumatic disorder with a striking female predominance. Numerous autoimmune phenomena are present in this disease, which ultimately result in organ damage. However, the specific cellular and humoral mechanisms underlying the immune dysfunction are not yet fully understood.

It is postulated that autoimmunity is based on the interaction of genetic predisposition, hormonal and environmental triggers that result in reduced tolerance to self-tissues. These phenomena could occur because of altered antigen presentation, abnormalities in B cell responses, increases in the function of T-helper cells, abnormal cytokine production, exaggerated effector responses, or loss of regulatory T cells or B cells. Abnormalities in all of these components of the immune response have been implicated to varying degrees in the pathogenesis of SLE.

This chapter will attempt to provide a “state-of-the-art” review of the evidence about the mechanisms underlying the pathology of SLE.

The authors Pedro Correia Azevedo and Grainne Murphy contributed equally to this project and should be considered co-first authors.

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References

  1. Lu LJ, Wallace DJ, Ishimori ML, Scofield RH, Weisman MH (2010) Male systemic lupus erythematosus: a review of sex disparities in this disease. Lupus 19:119–129

    Article  PubMed  Google Scholar 

  2. Johnson AE, Gordon C, Palmer RG, Bacon PA (1995) The prevalence and incidence of systemic lupus erythematosus in Birmingham, England: relationship to ethnicity and county of birth. Arthritis Rheum 38:551–558

    Article  CAS  PubMed  Google Scholar 

  3. Gladman DD, Urowitz MB (2007) Prognosis, mortality and morbidity in systemic lupus erythematosus. In: Wallace DJ, Hahn BH (eds) Dubois’ Lupus erythematosus, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1333–1353

    Google Scholar 

  4. Sullivan KE (2000) Genetic of systemic lupus erythematosus: clinical implications. Rheum Dis Clin North AM 26:229–256

    Article  CAS  PubMed  Google Scholar 

  5. Walport MJ (2002) Complement and systemic lupus erythematosus. Arthritis Res 4(Suppl 3):S279–S293

    Article  PubMed Central  PubMed  Google Scholar 

  6. Yang Y, Chung EK, Wu YL, Savelli SL, Nagaraja HN, Zhou B et al (2007) Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. Am J Hum Geneti 80:1037–1054

    Article  CAS  Google Scholar 

  7. Graham RR, Ortmann W, Rodine P, Espe K, Langefeld C, Lange E et al (2007) Specific combinations of HLA-DR2 and DR3 class II haplotypes contribute graded risk for disease susceptibility and autoantibodies in human SLE. Eur J Hum Genet 15:823–830

    Article  CAS  PubMed  Google Scholar 

  8. Rahman A, Isenberg D (2008) Systemic lupus erythematosus. N Eng J Med 358:929–939

    Article  CAS  Google Scholar 

  9. Harley JB, Alarcón-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL et al (2008) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40:204–210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW et al (2006) 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 38:550–555

    Article  CAS  PubMed  Google Scholar 

  11. Sigurdsson S, Nordmark G, Goring HHH, Lindroos K, Wiman AC, Sturfelt G et al (2005) Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5genes are associated with systemic lupus erythematosus. Am J Hum Gen 76:528–537

    Article  CAS  Google Scholar 

  12. Stern R, Fishman J, Brusman H, Kunkel HG (1977) Systemic lupus erythematosus associated with Klinefelter’s syndrome. Arthritis Rheum 20:18–22

    Article  CAS  PubMed  Google Scholar 

  13. Chanchoub G, Uz E, Maalej A (2009) Analysis of skewed X chromosome inactivation in females with rheumatoid arthritis and autoimmune thyroid diseases. Arthritis Res Ther 11:R106

    Article  Google Scholar 

  14. Hochberg MC (1997) Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  CAS  PubMed  Google Scholar 

  15. Cutolo M, Pizzorni C, Sulli A (2011) Vitamin D endocrine system involvement in autoimmune rheumatic diseases. Autoimmun Rev 11:84–87

    Article  CAS  PubMed  Google Scholar 

  16. Patel D, Richardson B (2013) Drug-induced lupus: etiology, pathogenesis, and clinical aspects. In: Wallace DJ, Hahn BH (eds) Dubois’ Lupus erythematosus, 8th edn. Elsevier, Philadelphia, pp 484–494

    Google Scholar 

  17. James JA, Kaufman KM, Farris AD, Taylor-Albert E, Lehman TJ, Harley JB (1997) An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J Clin Invest 100:3019–3026

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Netea MG, van der Meer JWH (2001) Mechanisms of disease—immunodeficiency and genetic defects of pattern-recognition receptors. N Eng J Med 364:60–70

    Google Scholar 

  19. Ronnblom LE, Alm GV, Oberg KE (1991) Autoimmunity after alpha-interferon therapy for malignant carcinoid-tumors. Ann Intern Med 115:178–183

    Article  CAS  PubMed  Google Scholar 

  20. Lahita RG, Bradlow HL, Kunkel HG, Fishman J (1979) Alterations of estrogen metabolism in systemic lupus erythematosus. Arthritis Rheum 22:1195–1198

    Article  CAS  PubMed  Google Scholar 

  21. Fromer JL (1950) The use of testosterone in chronic lupus erythematosus. Preliminary report. Lahey Clin Bul 8:13–17

    Google Scholar 

  22. Agnello V, Pariser K, Gell J, Gelfand J, Turksoy RN (1983) Preliminary observations on danazol therapy of systemic lupus erythematosus. Effects on DNA antibodies, thrombocytopaenia and complement. J Rheum 10:682–687

    CAS  PubMed  Google Scholar 

  23. Zen M, Ghiradello A, Iaccarino L, Tonon M, Campana C, Arienti S et al (2010) Hormones, immune response and pregnancy in healthy women and pregnancy. Swiss Med Weekly 140:187–201

    CAS  Google Scholar 

  24. Cohen-Solal JF, Jeganathan V, Grimaldi CM, Peeva E, Diamond B (2006) Sex hormones and SLE: influencing the fate of autoreactive B cells. Curr Top Microbiol Immunol 305:67–88

    CAS  PubMed  Google Scholar 

  25. Grimaldi CM, Cleary J, Dagtas AS, Moussai D, Diamond B (2002) Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest 109:1625–1633

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Siracusa MC, Overstreet MG, Housseau F, Scott AL, Klein SL (2008) 17 beta-oestradiol alters the activity of conventional and IFN-producing killer dendritic cells. J Immunol 180:1423–1431

    CAS  PubMed  Google Scholar 

  27. Hiran T (1998) IL-6 and its receptor. Int Rev Immunol 6:249–284

    Article  Google Scholar 

  28. Tackey E, Lipsky P, Illei G (2004) Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus 13:339–343

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Linker-Israeli M, Deans R, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR (1991) Elevated levels of endogenous IL-6 in systemic lupus erythematosus: a putative role in pathogenesis. J Immunol 147:117–123

    CAS  PubMed  Google Scholar 

  30. Tsai CY, Wu TH, Yu CL, Lu JY, Tsai YY (2000) Increased excretions of β2-microglobulin, IL-6 and IL-8 and decreased excretion of Tamm-Horsfall glycoprotein in urine of patients with active lupus nephritis. Nephron 85:207–214

    Article  CAS  PubMed  Google Scholar 

  31. Hirohata S, Kanai Y, Mitsuo A, Tokano Y, Hashimoto H (2009) Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A multicentre retrospective study. Clin Rheumatol 28:1319–1323

    Article  PubMed  Google Scholar 

  32. Herrera-Esparza R, Barbosa-Cisneros R, Villalobos-Hurtado R, Avalos-Diaz E (1998) Renal expression of IL-6 and TNF-α genes in lupus nephritis. Lupus 7:154–158

    Article  CAS  PubMed  Google Scholar 

  33. Mihara M, Takagi N, Takeda Y, Ohsugi Y (1998) IL-6 receptor blockade inhibits the onset of autoimmune kidney disease in NZB/Wf1 mice. Clin Exp Immunol 112:397–402

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Illei G, Yarboro C, Shirota Y, Daruwalla J, Tackey E, Takada K et al (2006) Tocilizumab (humanized anti-IL6 receptor antibody) in patients with systemic lupus erythematosus(SLE): safety, tolerability and preliminary efficacy. Arthritis Rheum 54:4043

    Google Scholar 

  35. Llorente L, Zou W, Levy Y, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J et al (1995) Role of Interleukin-10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181:839–844

    Article  CAS  PubMed  Google Scholar 

  36. Uhm WS, Na K, Song GW, Jung SS, Lee T, Park MH et al (2003) Cytokine balance in kidney tissue from lupus nephritis patients. Rheumatology (Oxford) 42:935–938

    Article  CAS  Google Scholar 

  37. Ronnelid J, Tejde A, Mathsson L, Nilsson-Ekdahl K, Nilsson B (2003) Immune complexes from SLE sera induce IL-10 production from normal peripheral blood mononuclear cells by an FcγRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE. Ann Rheum Dis 62:37–42

    Article  CAS  PubMed  Google Scholar 

  38. Sun KH, Yu CL, Tang SJ, Sun GH (2000) Monoclonal anti-double stranded DNA autoantibody stimulates the expression of IL-1β, IL-6, IL-8, IL-10 and TNF-α from normal human mononuclear cells involving in the lupus pathogenesis. Immunology 99:352–360

    Article  CAS  PubMed  Google Scholar 

  39. Llorente L, Richaud-Patin Y, Garcia-Padilla C, Claret E, Jakez-Ocampo J, Cardiel MH et al (2000) Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 43:1790–1800

    Article  CAS  PubMed  Google Scholar 

  40. Bengtsson G, Sturfelt G, Truedsson L, Blomberg J, Alm G, Vallin H et al (2000) Activation of type 1 Interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus 9:664–671

    Article  CAS  PubMed  Google Scholar 

  41. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ et al (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 100:2610–2615

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Ioannou Y, Isenberg DA (2000) Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy. Arthritis Rheum 43:1431–1442

    Article  CAS  PubMed  Google Scholar 

  43. Fitzgerald-Bocarsly P, Dai J, Singh S (2008) Plasmacytoid dendritic cells and type 1 IFN: 50 years of convergent history. Cytokine Growth Factor Rev 19:3–19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Lovgren T, Eloranta ML, Bave U, Alm GV, Rönnblom L (2004) Induction of interferon-α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum 50:1861–1872

    Article  PubMed  Google Scholar 

  45. Baccala R, Hoebe K, Kono DH, Beutler B, Theofilopoulos N (2007) TLR-dependent and TLR-independent pathways of Type 1 interferon induction in systemic autoimmunity. Nat Med 13:543–551

    Article  CAS  PubMed  Google Scholar 

  46. Le Bon A, Thompson C, Kamphuis E, Durand V, Rossmann C, Kalinke U et al (2006) Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type 1 IFN. J Immunol 176:2074–2078

    PubMed  Google Scholar 

  47. Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley B, Crow MK (2008) Association of the IRF5 risk haplotype with high serum interferon-α activity in systemic lupus erythematosus patients. Arthritis Rheum 58:2481–2487

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW et al (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357:977–986

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Hin Yap D, Neng Lai K (2010) Cytokines and their roles in the pathogenesis of systemic lupus erythematosus: from basics to recent advances. J Biomed 2010:365083. doi:10.1155/2010/365083. Epub 2010 May 6

    Google Scholar 

  50. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW (2008) Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th-17 mediated inflammation in auto-immunity. Clin Immunol 127:385–393

    Article  CAS  PubMed  Google Scholar 

  51. Zhang Z, Kyttaris VC, Tsokos GC (2009) The role of IL-23/IL-17 axis in lupus nephritis. Journal Immunol 183:3160–3169

    Article  CAS  Google Scholar 

  52. Crispin JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE et al (2008) Expanded double-negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. Journal Immunol 181:8761–8766

    CAS  Google Scholar 

  53. Mackay F, Schneider P (2009) Cracking the BAFF code. Nat Rev Immunol 9:491–502

    Article  CAS  PubMed  Google Scholar 

  54. Nardelli B, Belvedere O, Roschke V, Moore PA, Olsen HS, Migone TS et al (2001) Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood 97:198–204

    Article  CAS  PubMed  Google Scholar 

  55. Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P et al (2001) BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 293:2111–2114

    Article  Google Scholar 

  56. Cheema GS, Roschke V, Hilbert DM, Stohl W (2001) Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum 44:1313–1319

    Article  CAS  PubMed  Google Scholar 

  57. Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE et al (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377(9767):721–731

    Article  CAS  PubMed  Google Scholar 

  58. Jacob CO, Mcdevitt HO (1988) Tumour necrosis factor-alpha in murine autoimmune lupus nephritis. Nature 331:356–358

    Article  CAS  PubMed  Google Scholar 

  59. Mohan AK, Edwards ET, Cote TR, Siegal JN, Braun MM (2002) Drug-induced systemic lupus erythematosus and TNF-alpha blockers. Lancet 360:646

    Article  PubMed  Google Scholar 

  60. Aringer M, Graninger WB, Steiner G, Smolen JS (2004) Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an open label study. Arthritis Rheum 50:3161–3169

    Article  CAS  PubMed  Google Scholar 

  61. Ravirajan CT, Rahman MA, Papadaki L, Griffiths MH, Kalsi J, Martin AC et al (1998) Genetic, structural and functional properties of an IgG DNA-binding monoclonal antibody from a lupus patient with nephritis. Eur J Immunol 28:339–350, Erratum: Eur J Immunol 1999; 29: 3052

    Article  CAS  PubMed  Google Scholar 

  62. Okamura M, Kanayama Y, Amastu K, Negoro N, Kohda S, Takeda T et al (1993) Significance of enzyme linked immunosorbent assay (ELISA) for antibodies to double stranded and single stranded DNA in patients with lupus nephritis: correlation with severity of renal histology. Ann Rheum Dis 52:14–20

    Article  CAS  PubMed  Google Scholar 

  63. Rahman A (2004) Autoantibodies, lupus and the science of sabotage. Rheumatology (Oxford) 43:1326–1336

    Article  CAS  Google Scholar 

  64. Lu L, Kaliyaperumal A, Boumpas DT, Datta SK (1999) Major peptide autoepitopes for nucleosome-specific T cells of human lupus. J Clin Invest 104:345–355

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Kang HK, Chiang MY, Liu M, Ecklund D, Datta SK (2011) The histone peptide H471-94 is more effective than a cocktail of peptides epitopes in controlling lupus: immunoregulatory mechanisms. J Clin Immunol 31:379–394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Apostolidis SA, Lieberman LA, Kis-Toth K, Crispin JC, Tsokos GC (2011) The dysregulation of cytokine networks in systemic lupus erythematosus. J Interferon Cytokine Res 31:769–779

    Article  CAS  PubMed  Google Scholar 

  67. Gigante A, Gasperini ML, Afeltra A, Barbano B, Margiotta D, Cianci R et al (2011) Cytokines expression in SLE nephritis. Eur Rev Med Pharmacol Sci 15:15–24

    CAS  PubMed  Google Scholar 

  68. Cunninghame Graham DS, Morris DL, Bhangale TR, Criswell LA, Syvänen AC, Rönnblom L et al (2011) Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genet 7:e1002341

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Sawalha AH, Kaufman KM, Kelly JA, Adler AJ, Aberle T, Kilpatrick J et al (2008) Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus. Ann Rheum Dis 67:458–461

    Article  CAS  PubMed  Google Scholar 

  70. Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133:775–787

    Article  CAS  PubMed  Google Scholar 

  71. Buckner JH (2010) Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 10:849–859

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Yurasov SV, Wardermann H, Hammersen J, Pascual V, Meffre E, Nussenzweig MC (2004) Autoreactive B cells and immune tolerance alterations in peripheral blood of patients with systemic autoimmunity. Pediatr Res 292A

    Google Scholar 

  73. Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S et al (2009) Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induced long term remission through de novo generation of a juvenile and tolerant immune system. Blood 113:214–223

    Article  CAS  PubMed  Google Scholar 

  74. Nimmerjahn F, Ravetch JV (2007) Fc-receptors as regulators of immunity. Adv Immunol 96:179–204

    Article  CAS  PubMed  Google Scholar 

  75. Medina F, Segundo C, Campos-Caro A, González-García I, Brieva JA (2002) The heterogeneity shown by human plasma cells from tonsil, blood and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression. Blood 99:2154–2161

    Article  CAS  PubMed  Google Scholar 

  76. Odendahl M, Jacobi A, Hansen A, Feist E, Hiepe F, Burmester GR et al (2000) Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol 165:5970–5979

    CAS  PubMed  Google Scholar 

  77. Anolik JH, Aringer M (2005) New treatments for SLE: cell-depleting and anti-cytokine therapies. Best Pract Res Clin Rheumatol 19:859–878

    Article  CAS  PubMed  Google Scholar 

  78. Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X et al (2009) A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 41:1228–1233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR et al (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32:129–140

    Article  CAS  PubMed  Google Scholar 

  80. Bosma A, Abel-Gadir A, Isenberg DA, Jury EC, Mauri C (2012) Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells. Immunity 36:477–490

    Article  CAS  PubMed  Google Scholar 

  81. Koffler D, Schur PH, Kunkel HG (1967) Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med 126:607–624

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Isenberg DA, Shoenfeld Y, Walport M, Mackworth-Young C, Dudeney C, Todd-Pokropek A et al (1985) Detection of cross-reactive anti-DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives. Arthritis Rheum 28:999–1007

    Article  CAS  PubMed  Google Scholar 

  83. Ng KP, Manson JJ, Rahman A, Isenberg DA (2006) Association of anti-nucleosome antibodies with disease flare in serologically active clinically quiescent patients with systemic lupus erythematosus. Arthritis Rheum 55:900–904

    Article  CAS  PubMed  Google Scholar 

  84. Mannik M, Merrill CE, Stamps LD, Wener MH (2003) Multiple autoantibodies form the glomerular immune deposits in patients with systemic lupus erythematosus. J Rheumatol 30:1495–1504

    PubMed  Google Scholar 

  85. Sontheimer RD, Maddison PJ, Reichlin M, Jordan RE, Stastny P, Gilliam JN (1982) Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med 97:664–671

    Article  CAS  PubMed  Google Scholar 

  86. Kowal C, Degiorgio LA, Lee JY, Edgar MA, Huerta PT, Volpe BT et al (2006) Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci U S A 103:19854–19859

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Quisimoro FP (2007) Other serologic abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH (eds) Dubois’ Lupus erythematosus, 7th edn. Lippincott Williams and Wilkins, Philadelphia, pp 527–550

    Google Scholar 

  88. Pujol M, Ribera A, Vildarell M, Ordi J, Feliu E (1995) High prevalence of platelet auto-antibodies in patients with systemic lupus erythematosus. Br J Haematol 89:137–141

    Article  CAS  PubMed  Google Scholar 

  89. Berden JH, Licht R, van Bruggen MC, Tax WJ (1999) Role of nucleosomes for induction and glomerular binding of autoantibodies in lupus nephritis. Curr Opin Nephrol Hypertens 8:299–306

    Article  CAS  PubMed  Google Scholar 

  90. Kalaaji M, Fenton KA, Mortensen ES, Olsen R, Sturfelt G, Alm P et al (2007) Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis. Kidney Int 71:664–672

    Article  CAS  PubMed  Google Scholar 

  91. Kalaaji M, Mortensen E, Jorgensen L, Olsen R, Rekvig OP (2006) Nephritogenic lupus antibodies recognize glomerular basement membrane-associated chromatin fragments released from apoptotic intraglomerular cells. Am J Pathol 168:1779–1792

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Internal Medicine Department, Hospital Garcia de Orta, EPE, Almada, Portugal

    Pedro Correia Azevedo

  2. Department of Rheumatology, University College London, London, UK

    Grainne Murphy

  3. University College Hospital, London, UK

    David A. Isenberg M.D.

Authors
  1. Pedro Correia Azevedo
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  2. Grainne Murphy
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  3. David A. Isenberg M.D.
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Editors and Affiliations

  1. University of Exeter Medical School, Devon, United Kingdom

    Paul Eggleton

  2. Section of Immunology and Infection, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

    Frank J. Ward

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Azevedo, P.C., Murphy, G., Isenberg, D.A. (2014). Pathology of Systemic Lupus Erythematosus: The Challenges Ahead. In: Eggleton, P., Ward, F. (eds) Systemic Lupus Erythematosus. Methods in Molecular Biology, vol 1134. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0326-9_1

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