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Published in: Seminars in Immunopathology 3/2014

01-05-2014 | Review

The pathogenesis and diagnosis of systemic lupus erythematosus: still not resolved

Authors: Ole Petter Rekvig, Johan Van der Vlag

Published in: Seminars in Immunopathology | Issue 3/2014

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Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations affecting different tissues. A characteristic feature of SLE is the presence of autoantibodies against double-stranded (ds)DNA, histones and nucleosomes, and other chromatin components. SLE is a prototype type III hypersensitivity reaction. Local deposition of anti-nuclear antibodies in complex with released chromatin induces serious inflammatory conditions by activation of the complement system. The severe renal manifestation, lupus nephritis, is classified based on histological findings in renal biopsies. Apoptotic debris, including chromatin, is present in the extracellular matrix and circulation of patients with SLE. This may be due to an aberrant process of apoptosis and/or insufficient clearance of apoptotic cells/chromatin. The non-cleared apoptotic debris may lead to activation of both the innate and adaptive immune systems. In addition, an aberrant presentation of peptides by antigen-presenting cells, disturbed selection processes for lymphocytes, and deregulated lymphocyte responses may be involved in the development of autoimmunity. In the present review, we briefly will summarize current knowledge on the pathogenesis of SLE. We will also critically discuss and challenge central issues that need to be addressed in order to fully understand the pathogenic mechanisms involved in the development of SLE and in order to have an improved diagnosis for SLE. Disappointingly, in our opinion, there are still more questions than answers for the pathogenesis, diagnosis, and treatment of SLE.
Literature
1.
go back to reference Amital H, Heilweil M, Ulmansky R et al (2005) Treatment with a laminin-derived peptide suppresses lupus nephritis. J Immunol 175:5516–5523PubMed Amital H, Heilweil M, Ulmansky R et al (2005) Treatment with a laminin-derived peptide suppresses lupus nephritis. J Immunol 175:5516–5523PubMed
2.
go back to reference Andrzejewski C Jr, Rauch J, Lafer E et al (1981) Antigen-binding diversity and idiotypic cross-reactions among hybridoma autoantibodies to DNA. J Immunol 126:226–231PubMed Andrzejewski C Jr, Rauch J, Lafer E et al (1981) Antigen-binding diversity and idiotypic cross-reactions among hybridoma autoantibodies to DNA. J Immunol 126:226–231PubMed
3.
go back to reference Arbuckle MR, Mcclain MT, Rubertone MV et al (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 349:1526–1533PubMed Arbuckle MR, Mcclain MT, Rubertone MV et al (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 349:1526–1533PubMed
4.
5.
go back to reference Ardoin SP, Pisetsky DS (2008) The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles as intercellular mediators of inflammation. Mod Rheumatol 18:319–326PubMedCentralPubMed Ardoin SP, Pisetsky DS (2008) The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles as intercellular mediators of inflammation. Mod Rheumatol 18:319–326PubMedCentralPubMed
6.
go back to reference Ash Lerner A, Ginsberg Strauss M, Pewzner Jung Y et al (1997) Expression of an anti-DNA-associated VH gene in immunized and autoimmune mice. J Immunol 159:1508–1519PubMed Ash Lerner A, Ginsberg Strauss M, Pewzner Jung Y et al (1997) Expression of an anti-DNA-associated VH gene in immunized and autoimmune mice. J Immunol 159:1508–1519PubMed
7.
go back to reference Basnakian AG, Apostolov EO, Yin X et al (2005) Cisplatin nephrotoxicity is mediated by deoxyribonuclease I. J Am Soc Nephrol 16:697–702PubMed Basnakian AG, Apostolov EO, Yin X et al (2005) Cisplatin nephrotoxicity is mediated by deoxyribonuclease I. J Am Soc Nephrol 16:697–702PubMed
8.
go back to reference Berden JH (2003) Lupus nephritis: consequence of disturbed removal of apoptotic cells? Neth J Med 61:233–238PubMed Berden JH (2003) Lupus nephritis: consequence of disturbed removal of apoptotic cells? Neth J Med 61:233–238PubMed
9.
go back to reference Berden JH, Licht R, Van Bruggen MC et al (1999) Role of nucleosomes for induction and glomerular binding of autoantibodies in lupus nephritis. Curr Opin Nephrol Hypertens 8:299–306PubMed Berden JH, Licht R, Van Bruggen MC et al (1999) Role of nucleosomes for induction and glomerular binding of autoantibodies in lupus nephritis. Curr Opin Nephrol Hypertens 8:299–306PubMed
10.
go back to reference Boackle SA, Holers VM, Chen X et al (2001) Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein. Immunity 15:775–785PubMed Boackle SA, Holers VM, Chen X et al (2001) Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein. Immunity 15:775–785PubMed
11.
go back to reference Bolland S, Yim YS, Tus K et al (2002) Genetic modifiers of systemic lupus erythematosus in FcgammaRIIB(−/−) mice. J Exp Med 195:1167–1174PubMedCentralPubMed Bolland S, Yim YS, Tus K et al (2002) Genetic modifiers of systemic lupus erythematosus in FcgammaRIIB(−/−) mice. J Exp Med 195:1167–1174PubMedCentralPubMed
12.
go back to reference Boule MW, Broughton C, Mackay F et al (2004) Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes. J Exp Med 199:1631–1640PubMedCentralPubMed Boule MW, Broughton C, Mackay F et al (2004) Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes. J Exp Med 199:1631–1640PubMedCentralPubMed
13.
go back to reference Bouts YM, Wolthuis DFGJ, Dirkx MFM et al (2012) Apoptosis and NET formation in the pathogenesis of SLE. Autoimmunity 45:597–601PubMed Bouts YM, Wolthuis DFGJ, Dirkx MFM et al (2012) Apoptosis and NET formation in the pathogenesis of SLE. Autoimmunity 45:597–601PubMed
14.
go back to reference Brigido MM, Stollar BD (1991) Two induced anti-Z-DNA monoclonal antibodies use VH gene segments related to those of anti-DNA autoantibodies. J Immunol 146:2005–2009PubMed Brigido MM, Stollar BD (1991) Two induced anti-Z-DNA monoclonal antibodies use VH gene segments related to those of anti-DNA autoantibodies. J Immunol 146:2005–2009PubMed
15.
go back to reference Carroll P, Stafford D, Schwartz RS et al (1985) Murine monoclonal anti-DNA autoantibodies bind to endogenous bacteria. J Immunol 135:1086–1090PubMed Carroll P, Stafford D, Schwartz RS et al (1985) Murine monoclonal anti-DNA autoantibodies bind to endogenous bacteria. J Immunol 135:1086–1090PubMed
16.
go back to reference Casciola-Rosen L, Andrade F, Ulanet D et al (1999) Cleavage by granzyme B is strongly predictive of autoantigen status: Implications for initiation of autoimmunity. J Exp Med 190:815–825PubMedCentralPubMed Casciola-Rosen L, Andrade F, Ulanet D et al (1999) Cleavage by granzyme B is strongly predictive of autoantigen status: Implications for initiation of autoimmunity. J Exp Med 190:815–825PubMedCentralPubMed
17.
go back to reference Casciolarosen LA, Anhalt G, Rosen A (1994) Autoantigens targeted in systemic lupus-erythematosus are clustered in 2 populations of surface-structures on apoptotic keratinocytes. J Exp Med 179:1317–1330 Casciolarosen LA, Anhalt G, Rosen A (1994) Autoantigens targeted in systemic lupus-erythematosus are clustered in 2 populations of surface-structures on apoptotic keratinocytes. J Exp Med 179:1317–1330
18.
go back to reference Choi J, Kim ST, Craft J (2012) The pathogenesis of systemic lupus erythematosus—an update. Curr Opin Immunol 24:651–657PubMedCentralPubMed Choi J, Kim ST, Craft J (2012) The pathogenesis of systemic lupus erythematosus—an update. Curr Opin Immunol 24:651–657PubMedCentralPubMed
19.
go back to reference Dang H, Harbeck RJ (1982) A comparison of anti-DNA antibodies from serum and kidney eluates of NZB x NZW F1 mice. J Clin Lab Immunol 9:139–145PubMed Dang H, Harbeck RJ (1982) A comparison of anti-DNA antibodies from serum and kidney eluates of NZB x NZW F1 mice. J Clin Lab Immunol 9:139–145PubMed
20.
go back to reference Davies JM (1997) Molecular mimicry: can epitope mimicry induce autoimmune disease? Immunol Cell Biol 75:113–126PubMed Davies JM (1997) Molecular mimicry: can epitope mimicry induce autoimmune disease? Immunol Cell Biol 75:113–126PubMed
21.
go back to reference Deocharan B, Qing X, Lichauco J et al (2002) Alpha-actinin is a cross-reactive renal target for pathogenic anti-DNA antibodies. J Immunol 168:3072–3078PubMed Deocharan B, Qing X, Lichauco J et al (2002) Alpha-actinin is a cross-reactive renal target for pathogenic anti-DNA antibodies. J Immunol 168:3072–3078PubMed
22.
go back to reference Desai DD, Krishnan MR, Swindle JT et al (1993) Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice. J Immunol 151:1614–1626PubMed Desai DD, Krishnan MR, Swindle JT et al (1993) Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice. J Immunol 151:1614–1626PubMed
23.
go back to reference Diamond B, Volpe BT (2012) A model for lupus brain disease. Immunol Rev 248:56–67PubMed Diamond B, Volpe BT (2012) A model for lupus brain disease. Immunol Rev 248:56–67PubMed
24.
go back to reference Dieker JW, Fransen JH, Van Bavel CC et al (2007) Apoptosis-induced acetylation of histones is pathogenic in systemic lupus erythematosus. Arthritis Rheum 56:1921–1933PubMed Dieker JW, Fransen JH, Van Bavel CC et al (2007) Apoptosis-induced acetylation of histones is pathogenic in systemic lupus erythematosus. Arthritis Rheum 56:1921–1933PubMed
25.
go back to reference Dieker JW, Van der Vlag J, Berden JH (2004) Deranged removal of apoptotic cells: its role in the genesis of lupus. Nephrol Dial Transplant 19:282–285PubMed Dieker JW, Van der Vlag J, Berden JH (2004) Deranged removal of apoptotic cells: its role in the genesis of lupus. Nephrol Dial Transplant 19:282–285PubMed
26.
go back to reference Dieker JW, Van der Vlag J, Berden JH (2002) Triggers for anti-chromatin autoantibody production in SLE. Lupus 11:856–864PubMed Dieker JW, Van der Vlag J, Berden JH (2002) Triggers for anti-chromatin autoantibody production in SLE. Lupus 11:856–864PubMed
27.
go back to reference Doyle HA, Mamula MJ (2005) Posttranslational modifications of self-antigens. Ann N Y Acad Sci 1050:1–9PubMed Doyle HA, Mamula MJ (2005) Posttranslational modifications of self-antigens. Ann N Y Acad Sci 1050:1–9PubMed
28.
go back to reference Ehrenstein MR, Katz DR, Griffiths MH et al (1995) Human IgG anti-DNA antibodies deposit in kidneys and induce proteinuria in SCID mice. Kidney Int 48:705–711PubMed Ehrenstein MR, Katz DR, Griffiths MH et al (1995) Human IgG anti-DNA antibodies deposit in kidneys and induce proteinuria in SCID mice. Kidney Int 48:705–711PubMed
29.
go back to reference Fairhurst AM, Hwang SH, Wang A et al (2008) Yaa autoimmune phenotypes are conferred by overexpression of TLR7. Eur J Immunol 38:1971–1978PubMedCentralPubMed Fairhurst AM, Hwang SH, Wang A et al (2008) Yaa autoimmune phenotypes are conferred by overexpression of TLR7. Eur J Immunol 38:1971–1978PubMedCentralPubMed
30.
go back to reference Fenton K, Fismen S, Hedberg A et al (2009) Anti-dsDNA antibodies promote initiation, and acquired loss of renal Dnase1 promotes progression of lupus nephritis in autoimmune (NZBxNZW)F1 mice. PLoS One 4:e8474PubMedCentralPubMed Fenton K, Fismen S, Hedberg A et al (2009) Anti-dsDNA antibodies promote initiation, and acquired loss of renal Dnase1 promotes progression of lupus nephritis in autoimmune (NZBxNZW)F1 mice. PLoS One 4:e8474PubMedCentralPubMed
31.
go back to reference Fenton KA, Tommeras B, Marion TN et al (2010) Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice. Autoimmunity 43:179–188PubMed Fenton KA, Tommeras B, Marion TN et al (2010) Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice. Autoimmunity 43:179–188PubMed
32.
go back to reference Fismen S, Hedberg A, Fenton K et al (2009) Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis. Lupus 18:597–607 Fismen S, Hedberg A, Fenton K et al (2009) Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis. Lupus 18:597–607
33.
go back to reference Fismen S, Thiyagarajan D, Seredkina N et al. (2013) Impact of the tumor necrosis factor receptor-associated protein 1 (Trap1) on renal DNaseI shutdown and on progression of murine and human lupus nephritis. Am J Pathol 182:688--700 Fismen S, Thiyagarajan D, Seredkina N et al. (2013) Impact of the tumor necrosis factor receptor-associated protein 1 (Trap1) on renal DNaseI shutdown and on progression of murine and human lupus nephritis. Am J Pathol 182:688--700
35.
go back to reference Fransen JH, Hilbrands LB, Jacobs CW et al (2009) Both early and late apoptotic blebs are taken up by DC and induce IL-6 production. Autoimmunity 42:325–327PubMed Fransen JH, Hilbrands LB, Jacobs CW et al (2009) Both early and late apoptotic blebs are taken up by DC and induce IL-6 production. Autoimmunity 42:325–327PubMed
36.
go back to reference Fransen JH, Hilbrands LB, Ruben J et al (2009) Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin-17. Arthritis Rheum 60:2304–2313PubMed Fransen JH, Hilbrands LB, Ruben J et al (2009) Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin-17. Arthritis Rheum 60:2304–2313PubMed
37.
go back to reference Fransen JH, Hilbrands LB, Koeter CM, Berden JH, Van der Vlag J. (2009) The role of apoptosis and removal of apoptotic cells in the genesis of systemic lupus erythematosus. Arch Med Sci 5:S466-S477 Fransen JH, Hilbrands LB, Koeter CM, Berden JH, Van der Vlag J. (2009) The role of apoptosis and removal of apoptotic cells in the genesis of systemic lupus erythematosus. Arch Med Sci 5:S466-S477
38.
go back to reference Gaipl US, Sheriff A, Franz S et al (2006) Inefficient clearance of dying cells and autoreactivity. Curr Top Microbiol Immunol 305:161–176PubMed Gaipl US, Sheriff A, Franz S et al (2006) Inefficient clearance of dying cells and autoreactivity. Curr Top Microbiol Immunol 305:161–176PubMed
39.
go back to reference Garcia-Romo GS, Caielli S, Vega B et al (2011) Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med 3:73ra20PubMedCentralPubMed Garcia-Romo GS, Caielli S, Vega B et al (2011) Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med 3:73ra20PubMedCentralPubMed
40.
go back to reference Garrett-Sinha LA, John S, Gaffen SL (2008) IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol 20:519–525PubMed Garrett-Sinha LA, John S, Gaffen SL (2008) IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol 20:519–525PubMed
41.
go back to reference Gilkeson GS, Grudier JP, Karounos DG et al (1989) Induction of anti-double stranded DNA antibodies in normal mice by immunization with bacterial DNA. J Immunol 142:1482–1486PubMed Gilkeson GS, Grudier JP, Karounos DG et al (1989) Induction of anti-double stranded DNA antibodies in normal mice by immunization with bacterial DNA. J Immunol 142:1482–1486PubMed
42.
go back to reference Gilkeson GS, Ruiz P, Howell D et al (1993) Induction of immune-mediated glomerulonephritis in normal mice immunized with bacterial DNA. Clin Immunol Immunopathol 68:283–292PubMed Gilkeson GS, Ruiz P, Howell D et al (1993) Induction of immune-mediated glomerulonephritis in normal mice immunized with bacterial DNA. Clin Immunol Immunopathol 68:283–292PubMed
43.
go back to reference Green MC, Shultz LD (1975) Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J Hered 66:250–258PubMed Green MC, Shultz LD (1975) Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J Hered 66:250–258PubMed
44.
go back to reference Griffith J, Bleyman M, Rauch CA et al (1986) Visualization of the bent helix in kinetoplast DNA by electron microscopy. Cell 46:717–724PubMed Griffith J, Bleyman M, Rauch CA et al (1986) Visualization of the bent helix in kinetoplast DNA by electron microscopy. Cell 46:717–724PubMed
45.
go back to reference Grootscholten C, Van Bruggen MC, Van Der Pijl JW et al (2003) Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis. Arthritis Rheum 48:1355–1362PubMed Grootscholten C, Van Bruggen MC, Van Der Pijl JW et al (2003) Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis. Arthritis Rheum 48:1355–1362PubMed
46.
go back to reference Guerra SG, Vyse TJ, Cunninghame Graham DS (2012) The genetics of lupus: a functional perspective. Arthritis Res Ther 14:211PubMedCentralPubMed Guerra SG, Vyse TJ, Cunninghame Graham DS (2012) The genetics of lupus: a functional perspective. Arthritis Res Ther 14:211PubMedCentralPubMed
47.
48.
go back to reference Haugbro K, Nossent JC, Winkler T et al (2004) Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity. Ann Rheum Dis 63:386–394PubMedCentralPubMed Haugbro K, Nossent JC, Winkler T et al (2004) Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity. Ann Rheum Dis 63:386–394PubMedCentralPubMed
49.
go back to reference Hedberg A, Fismen S, Fenton KA et al (2011) Heparin exerts a dual effect on murine lupus nephritis by enhancing enzymatic chromatin degradation and preventing chromatin binding in glomerular membranes. Arthritis Rheum 63:1065–1075PubMed Hedberg A, Fismen S, Fenton KA et al (2011) Heparin exerts a dual effect on murine lupus nephritis by enhancing enzymatic chromatin degradation and preventing chromatin binding in glomerular membranes. Arthritis Rheum 63:1065–1075PubMed
50.
go back to reference Hedberg A, Mortensen ES, Rekvig OP (2011) Chromatin as a target antigen in human and murine lupus nephritis. Arthritis Res Ther 13:214PubMedCentralPubMed Hedberg A, Mortensen ES, Rekvig OP (2011) Chromatin as a target antigen in human and murine lupus nephritis. Arthritis Res Ther 13:214PubMedCentralPubMed
51.
go back to reference Herrmann M, Voll RE, Zoller OM et al (1998) Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 41:1241–1250PubMed Herrmann M, Voll RE, Zoller OM et al (1998) Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 41:1241–1250PubMed
52.
go back to reference Hobson DJ, Wei W, Steinmetz LM et al (2012) RNA polymerase II collision interrupts convergent transcription. Mol Cell 48:365–374PubMedCentralPubMed Hobson DJ, Wei W, Steinmetz LM et al (2012) RNA polymerase II collision interrupts convergent transcription. Mol Cell 48:365–374PubMedCentralPubMed
53.
go back to reference Huerta PT, Kowal C, Degiorgio LA et al (2006) Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci U S A 103:678–683PubMedCentralPubMed Huerta PT, Kowal C, Degiorgio LA et al (2006) Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci U S A 103:678–683PubMedCentralPubMed
54.
go back to reference Isenberg D, Lesavre P (2007) Lupus nephritis: assessing the evidence, considering the future. Lupus 16:210–211PubMed Isenberg D, Lesavre P (2007) Lupus nephritis: assessing the evidence, considering the future. Lupus 16:210–211PubMed
55.
go back to reference Isenberg DA, Ehrenstein MR, Longhurst C et al (1994) The origin, sequence, structure, and consequences of developing anti-DNA antibodies. A human perspective. Arthritis Rheum 37:169–180PubMed Isenberg DA, Ehrenstein MR, Longhurst C et al (1994) The origin, sequence, structure, and consequences of developing anti-DNA antibodies. A human perspective. Arthritis Rheum 37:169–180PubMed
56.
go back to reference Isenberg DA, Manson JJ, Ehrenstein MR et al (2007) Fifty years of anti-ds DNA antibodies: are we approaching journey's end? Rheumatology (Oxford) 46:1052–1056 Isenberg DA, Manson JJ, Ehrenstein MR et al (2007) Fifty years of anti-ds DNA antibodies: are we approaching journey's end? Rheumatology (Oxford) 46:1052–1056
57.
go back to reference Izui S (1990) Autoimmune accelerating genes, lpr and Yaa, in murine systemic lupus erythematosus. Autoimmunity 6:113–129PubMed Izui S (1990) Autoimmune accelerating genes, lpr and Yaa, in murine systemic lupus erythematosus. Autoimmunity 6:113–129PubMed
58.
go back to reference Izui S, Kelley VE, Masuda K et al (1984) Induction of various autoantibodies by mutant gene lpr in several strains of mice. J Immunol 133:227–233PubMed Izui S, Kelley VE, Masuda K et al (1984) Induction of various autoantibodies by mutant gene lpr in several strains of mice. J Immunol 133:227–233PubMed
59.
go back to reference Jang YJ, Stollar BD (2003) Anti-DNA antibodies: aspects of structure and pathogenicity. Cell Mol Life Sci 60:309–320PubMed Jang YJ, Stollar BD (2003) Anti-DNA antibodies: aspects of structure and pathogenicity. Cell Mol Life Sci 60:309–320PubMed
60.
go back to reference Balow JE, Boumpas DT, Ausin HA (1999) Systemic lupus erythematosus and the kidney. In: Lahiota RG (ed) Systemic lupus erythematosus, 3rd edn. Academic, San Diego, pp 657–685 Balow JE, Boumpas DT, Ausin HA (1999) Systemic lupus erythematosus and the kidney. In: Lahiota RG (ed) Systemic lupus erythematosus, 3rd edn. Academic, San Diego, pp 657–685
61.
go back to reference Kalaaji M, Fenton KA, Mortensen ES et al (2007) Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis. Kidney Int 71:664–672PubMed Kalaaji M, Fenton KA, Mortensen ES et al (2007) Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis. Kidney Int 71:664–672PubMed
62.
go back to reference Kalaaji M, Mortensen E, Jorgensen L et al (2006) Nephritogenic lupus antibodies recognize glomerular basement membrane-associated chromatin fragments released from apoptotic intraglomerular cells. Am J Pathol 168:1779–1792PubMedCentralPubMed Kalaaji M, Mortensen E, Jorgensen L et al (2006) Nephritogenic lupus antibodies recognize glomerular basement membrane-associated chromatin fragments released from apoptotic intraglomerular cells. Am J Pathol 168:1779–1792PubMedCentralPubMed
63.
go back to reference Kalaaji M, Sturfelt G, Mjelle JE et al (2006) Critical comparative analyses of anti-alpha-actinin and glomerulus-bound antibodies in human and murine lupus nephritis. Arthritis Rheum 54:914–926PubMed Kalaaji M, Sturfelt G, Mjelle JE et al (2006) Critical comparative analyses of anti-alpha-actinin and glomerulus-bound antibodies in human and murine lupus nephritis. Arthritis Rheum 54:914–926PubMed
64.
go back to reference Kalsi JK, Martin AC, Hirabayashi Y et al (1996) Functional and modelling studies of the binding of human monoclonal anti-DNA antibodies to DNA. Mol Immunol 33:471–483PubMed Kalsi JK, Martin AC, Hirabayashi Y et al (1996) Functional and modelling studies of the binding of human monoclonal anti-DNA antibodies to DNA. Mol Immunol 33:471–483PubMed
66.
go back to reference Krishnan MR, Wang C, Marion TN (2012) Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice. Kidney Int 82:184–192PubMedCentralPubMed Krishnan MR, Wang C, Marion TN (2012) Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice. Kidney Int 82:184–192PubMedCentralPubMed
67.
go back to reference Kruse K, Janko C, Urbonaviciute V et al (2010) Inefficient clearance of dying cells in patients with SLE: anti-dsDNA autoantibodies, MFG-E8, HMGB-1 and other players. Apoptosis Int J Program Cell Death 15:1098–1113 Kruse K, Janko C, Urbonaviciute V et al (2010) Inefficient clearance of dying cells in patients with SLE: anti-dsDNA autoantibodies, MFG-E8, HMGB-1 and other players. Apoptosis Int J Program Cell Death 15:1098–1113
68.
go back to reference Lafer EM, Rauch J, Andrzejewski C Jr et al (1981) Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. J Exp Med 153:897–909PubMed Lafer EM, Rauch J, Andrzejewski C Jr et al (1981) Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. J Exp Med 153:897–909PubMed
69.
go back to reference Lande R, Ganguly D, Facchinetti V et al (2011) Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci Transl Med 3:73ra19PubMedCentralPubMed Lande R, Ganguly D, Facchinetti V et al (2011) Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci Transl Med 3:73ra19PubMedCentralPubMed
70.
go back to reference Lefkowith JB, Gilkeson GS (1996) Nephritogenic autoantibodies in lupus: current concepts and continuing controversies. Arthritis Rheum 39:894–903PubMed Lefkowith JB, Gilkeson GS (1996) Nephritogenic autoantibodies in lupus: current concepts and continuing controversies. Arthritis Rheum 39:894–903PubMed
71.
go back to reference Lerner J, Ginsberg M, Marion TN et al (1997) Analysis of B/W-DNA 16 V(H) gene expression following DNA-peptide immunization. Lupus 6:328–329PubMed Lerner J, Ginsberg M, Marion TN et al (1997) Analysis of B/W-DNA 16 V(H) gene expression following DNA-peptide immunization. Lupus 6:328–329PubMed
72.
go back to reference Licht R, Dieker JW, Jacobs CW et al (2004) Decreased phagocytosis of apoptotic cells in diseased SLE mice. J Autoimmun 22:139–145PubMed Licht R, Dieker JW, Jacobs CW et al (2004) Decreased phagocytosis of apoptotic cells in diseased SLE mice. J Autoimmun 22:139–145PubMed
73.
go back to reference Liu Z, Davidson A (2012) Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med 18:871–882PubMedCentralPubMed Liu Z, Davidson A (2012) Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med 18:871–882PubMedCentralPubMed
74.
go back to reference Luijten RKMC, Fritsch-Stork RD, Bijlsma JWJ et al (2013) The use of glucocorticoids in systemic lupus erythematosus. After 60 years still more an art than science. Autoimmun Rev 12:617–628PubMed Luijten RKMC, Fritsch-Stork RD, Bijlsma JWJ et al (2013) The use of glucocorticoids in systemic lupus erythematosus. After 60 years still more an art than science. Autoimmun Rev 12:617–628PubMed
75.
go back to reference Khalil M, Spatz L, Diamond B (1999) Anti-DNA antibodies. In: Lahita RG (ed) Systemic lupus erythematosus, 3rd edn. Academic, San Diego, pp 197–217 Khalil M, Spatz L, Diamond B (1999) Anti-DNA antibodies. In: Lahita RG (ed) Systemic lupus erythematosus, 3rd edn. Academic, San Diego, pp 197–217
76.
go back to reference Madaio MP, Hodder S, Schwartz RS et al (1984) Responsiveness of autoimmune and normal mice to nucleic acid antigens. J Immunol 132:872–876PubMed Madaio MP, Hodder S, Schwartz RS et al (1984) Responsiveness of autoimmune and normal mice to nucleic acid antigens. J Immunol 132:872–876PubMed
77.
go back to reference Mageed RA, Zack DJ (2002) Cross-reactivity and pathogenicity of anti-DNA autoantibodies in systemic lupus erythematosus. Lupus 11:783–786PubMed Mageed RA, Zack DJ (2002) Cross-reactivity and pathogenicity of anti-DNA autoantibodies in systemic lupus erythematosus. Lupus 11:783–786PubMed
78.
go back to reference Mak A, Isenberg DA, Lau CS (2013) Global trends, potential mechanisms and early detection of organ damage in SLE. Nat Rev Rheumatol 9:301–310PubMed Mak A, Isenberg DA, Lau CS (2013) Global trends, potential mechanisms and early detection of organ damage in SLE. Nat Rev Rheumatol 9:301–310PubMed
79.
go back to reference Meacock R, Dale N, Harrison MJ (2013) The humanistic and economic burden of systemic lupus erythematosus: a systematic review. Pharmacoeconomics 31:49–61PubMed Meacock R, Dale N, Harrison MJ (2013) The humanistic and economic burden of systemic lupus erythematosus: a systematic review. Pharmacoeconomics 31:49–61PubMed
80.
go back to reference Mjelle JE, Kalaaji M, Rekvig OP (2009) Exposure of chromatin and not high affinity for dsDNA determines the nephritogenic impact of anti-dsDNA antibodies in (NZBxNZW)F1 mice. Autoimmunity 42:104–111PubMed Mjelle JE, Kalaaji M, Rekvig OP (2009) Exposure of chromatin and not high affinity for dsDNA determines the nephritogenic impact of anti-dsDNA antibodies in (NZBxNZW)F1 mice. Autoimmunity 42:104–111PubMed
81.
go back to reference Mjelle JE, Rekvig OP, Fenton KA (2007) Nucleosomes possess a high affinity for glomerular laminin and collagen IV and bind nephritogenic antibodies in murine lupus-like nephritis. Ann Rheum Dis 66:1661–1668PubMedCentralPubMed Mjelle JE, Rekvig OP, Fenton KA (2007) Nucleosomes possess a high affinity for glomerular laminin and collagen IV and bind nephritogenic antibodies in murine lupus-like nephritis. Ann Rheum Dis 66:1661–1668PubMedCentralPubMed
82.
go back to reference Moens U, Seternes OM, Hey AW et al (1995) In vivo expression of a single viral DNA-binding protein generates systemic lupus erythematosus-related autoimmunity to double-stranded DNA and histones. Proc Natl Acad Sci U S A 92:12393–12397PubMedCentralPubMed Moens U, Seternes OM, Hey AW et al (1995) In vivo expression of a single viral DNA-binding protein generates systemic lupus erythematosus-related autoimmunity to double-stranded DNA and histones. Proc Natl Acad Sci U S A 92:12393–12397PubMedCentralPubMed
83.
go back to reference Mortensen ES, Fenton KA, Rekvig OP (2008) Lupus nephritis: the central role of nucleosomes revealed. Am J Pathol 172:275–283PubMedCentralPubMed Mortensen ES, Fenton KA, Rekvig OP (2008) Lupus nephritis: the central role of nucleosomes revealed. Am J Pathol 172:275–283PubMedCentralPubMed
84.
go back to reference Mortensen ES, Rekvig OP (2009) Nephritogenic potential of anti-DNA antibodies against necrotic nucleosomes. J Am Soc Nephrol 20:696–704PubMed Mortensen ES, Rekvig OP (2009) Nephritogenic potential of anti-DNA antibodies against necrotic nucleosomes. J Am Soc Nephrol 20:696–704PubMed
85.
go back to reference Mostoslavsky G, Fischel R, Yachimovich N et al (2001) Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry. Eur J Immunol 31:1221–1227PubMed Mostoslavsky G, Fischel R, Yachimovich N et al (2001) Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry. Eur J Immunol 31:1221–1227PubMed
86.
go back to reference Munoz LE, Janko C, Schulze C et al (2010) Autoimmunity and chronic inflammation—two clearance-related steps in the etiopathogenesis of SLE. Autoimmun Rev 10:38–42PubMed Munoz LE, Janko C, Schulze C et al (2010) Autoimmunity and chronic inflammation—two clearance-related steps in the etiopathogenesis of SLE. Autoimmun Rev 10:38–42PubMed
87.
go back to reference Munoz LE, Lauber K, Schiller M et al (2010) The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 6:280–289PubMed Munoz LE, Lauber K, Schiller M et al (2010) The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 6:280–289PubMed
88.
go back to reference Munoz LE, Van Bavel C, Franz S et al (2008) Apoptosis in the pathogenesis of systemic lupus erythematosus. Lupus 17:371–375PubMed Munoz LE, Van Bavel C, Franz S et al (2008) Apoptosis in the pathogenesis of systemic lupus erythematosus. Lupus 17:371–375PubMed
89.
go back to reference Ohteki T, Hessel A, Bachmann MF et al (1999) Identification of a cross-reactive self ligand in virus-mediated autoimmunity. Eur J Immunol 29:2886–2896PubMed Ohteki T, Hessel A, Bachmann MF et al (1999) Identification of a cross-reactive self ligand in virus-mediated autoimmunity. Eur J Immunol 29:2886–2896PubMed
90.
go back to reference Oldstone MB (1987) Molecular mimicry and autoimmune disease [published erratum appears in Cell 1987 Dec 4;51(5):878]. Cell 50:819–820PubMed Oldstone MB (1987) Molecular mimicry and autoimmune disease [published erratum appears in Cell 1987 Dec 4;51(5):878]. Cell 50:819–820PubMed
91.
go back to reference Petri M, Orbai AM, Alarcon GS et al (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686PubMedCentralPubMed Petri M, Orbai AM, Alarcon GS et al (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686PubMedCentralPubMed
92.
go back to reference Pisetsky DS (2012) Antinuclear antibodies in rheumatic disease: a proposal for a function-based classification. Scand J Immunol 76:223–228PubMed Pisetsky DS (2012) Antinuclear antibodies in rheumatic disease: a proposal for a function-based classification. Scand J Immunol 76:223–228PubMed
93.
go back to reference Pisetsky DS (1997) Specificity and immunochemical properties of antibodies to bacterial DNA. Methods 11:55–61PubMed Pisetsky DS (1997) Specificity and immunochemical properties of antibodies to bacterial DNA. Methods 11:55–61PubMed
94.
go back to reference Pisitkun P, Deane JA, Difilippantonio MJ et al (2006) Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312:1669–1672PubMed Pisitkun P, Deane JA, Difilippantonio MJ et al (2006) Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312:1669–1672PubMed
95.
go back to reference Price JV, Tangsombatvisit S, Xu GY et al (2012) On silico peptide microarrays for high-resolution mapping of antibody epitopes and diverse protein-protein interactions. Nat Med 18:1434−1440 Price JV, Tangsombatvisit S, Xu GY et al (2012) On silico peptide microarrays for high-resolution mapping of antibody epitopes and diverse protein-protein interactions. Nat Med 18:1434−1440
96.
go back to reference Punaro MG (2013) The treatment of systemic lupus proliferative nephritis. Pediatr Nephrol 28:2069–2078PubMed Punaro MG (2013) The treatment of systemic lupus proliferative nephritis. Pediatr Nephrol 28:2069–2078PubMed
97.
go back to reference Putterman C, Diamond B (1998) Immunization with a peptide surrogate for double-stranded DNA (dsDNA) induces autoantibody production and renal immunoglobulin deposition. J Exp Med 188:29–38PubMedCentralPubMed Putterman C, Diamond B (1998) Immunization with a peptide surrogate for double-stranded DNA (dsDNA) induces autoantibody production and renal immunoglobulin deposition. J Exp Med 188:29–38PubMedCentralPubMed
98.
go back to reference Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939PubMed Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939PubMed
99.
go back to reference Ray SK, Putterman C, Diamond B (1996) Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease. Proc Natl Acad Sci U S A 93:2019–2024PubMedCentralPubMed Ray SK, Putterman C, Diamond B (1996) Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease. Proc Natl Acad Sci U S A 93:2019–2024PubMedCentralPubMed
100.
go back to reference Rekvig OP, Moens U, Sundsfjord A et al (1997) Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen. A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors. J Clin Invest 99:2045–2054PubMedCentralPubMed Rekvig OP, Moens U, Sundsfjord A et al (1997) Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen. A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors. J Clin Invest 99:2045–2054PubMedCentralPubMed
101.
go back to reference Rekvig OP, Nossent JC (2003) Anti-double-stranded DNA antibodies, nucleosomes, and systemic lupus erythematosus: a time for new paradigms? Arthritis Rheum 48:300–312PubMed Rekvig OP, Nossent JC (2003) Anti-double-stranded DNA antibodies, nucleosomes, and systemic lupus erythematosus: a time for new paradigms? Arthritis Rheum 48:300–312PubMed
102.
go back to reference Ronnblom L, Alm GV, Eloranta ML (2009) Type I interferon and lupus. Curr Opin Rheumatol 21:471–477PubMed Ronnblom L, Alm GV, Eloranta ML (2009) Type I interferon and lupus. Curr Opin Rheumatol 21:471–477PubMed
103.
go back to reference Rumore PM, Steinman CR (1990) Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone. J Clin Invest 86:69–74PubMedCentralPubMed Rumore PM, Steinman CR (1990) Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone. J Clin Invest 86:69–74PubMedCentralPubMed
104.
go back to reference Sabbaga J, Line SR, Potocnjak P et al (1989) A murine nephritogenic monoclonal anti-DNA autoantibody binds directly to mouse laminin, the major non-collagenous protein component of the glomerular basement membrane. Eur J Immunol 19:137–143PubMed Sabbaga J, Line SR, Potocnjak P et al (1989) A murine nephritogenic monoclonal anti-DNA autoantibody binds directly to mouse laminin, the major non-collagenous protein component of the glomerular basement membrane. Eur J Immunol 19:137–143PubMed
105.
go back to reference Seredkina N, Rekvig OP (2011) Acquired loss of renal nuclease activity is restricted to DNasel and is an organ-selective feature in murine lupus nephritis. Am J Pathol 179:1120–1128PubMedCentralPubMed Seredkina N, Rekvig OP (2011) Acquired loss of renal nuclease activity is restricted to DNasel and is an organ-selective feature in murine lupus nephritis. Am J Pathol 179:1120–1128PubMedCentralPubMed
106.
go back to reference Seredkina N, Van der Vlag J, Berden J et al (2013) Lupus nephritis: enigmas, conflicting models and an emerging concept. Mol Med 19:161–169PubMedCentralPubMed Seredkina N, Van der Vlag J, Berden J et al (2013) Lupus nephritis: enigmas, conflicting models and an emerging concept. Mol Med 19:161–169PubMedCentralPubMed
107.
go back to reference Seredkina N, Zykova SN, Rekvig OP (2009) Progression of murine lupus nephritis is linked to acquired renal Dnase1 deficiency and not to up-regulated apoptosis. Am J Pathol 175:97–106PubMedCentralPubMed Seredkina N, Zykova SN, Rekvig OP (2009) Progression of murine lupus nephritis is linked to acquired renal Dnase1 deficiency and not to up-regulated apoptosis. Am J Pathol 175:97–106PubMedCentralPubMed
108.
109.
go back to reference Shilatifard A (2004) Transcriptional elongation control by RNA polymerase II: a new frontier. Biochim Biophys Acta 1677:79–86PubMed Shilatifard A (2004) Transcriptional elongation control by RNA polymerase II: a new frontier. Biochim Biophys Acta 1677:79–86PubMed
110.
go back to reference Shlomchik M, Mascelli M, Shan H et al (1990) Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med 171:265–292PubMed Shlomchik M, Mascelli M, Shan H et al (1990) Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med 171:265–292PubMed
111.
go back to reference Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB et al (1987) The role of clonal selection and somatic mutation in autoimmunity. Nature 328:805–811PubMed Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB et al (1987) The role of clonal selection and somatic mutation in autoimmunity. Nature 328:805–811PubMed
112.
go back to reference Stollar BD (1986) Antibodies to DNA. CRC Crit Rev Biochem 20:1–36PubMed Stollar BD (1986) Antibodies to DNA. CRC Crit Rev Biochem 20:1–36PubMed
113.
114.
go back to reference Sundar K, Jacques S, Gottlieb P et al (2004) 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 23:127–140PubMed Sundar K, Jacques S, Gottlieb P et al (2004) 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 23:127–140PubMed
115.
go back to reference Svejstrup JQ (2013) RNA polymerase II transcript elongation. Biochim Biophys Acta 1829:1PubMed Svejstrup JQ (2013) RNA polymerase II transcript elongation. Biochim Biophys Acta 1829:1PubMed
116.
go back to reference Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMed Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMed
117.
go back to reference Thiyagarajan D, Fismen S, Seredkina N et al (2012) Silencing of renal DNaseI in murine lupus nephritis imposes exposure of large chromatin fragments and activation of toll like receptors and the Clec4e. PLoS One 7:e34080PubMedCentralPubMed Thiyagarajan D, Fismen S, Seredkina N et al (2012) Silencing of renal DNaseI in murine lupus nephritis imposes exposure of large chromatin fragments and activation of toll like receptors and the Clec4e. PLoS One 7:e34080PubMedCentralPubMed
118.
go back to reference Tillman DM, Jou NT, Hill RJ et al (1992) Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. J Exp Med 176:761–779PubMed Tillman DM, Jou NT, Hill RJ et al (1992) Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. J Exp Med 176:761–779PubMed
119.
go back to reference Tsokos GC (2011) Mechanisms of disease systemic lupus erythematosus. N Engl J Med 365:2110–2121PubMed Tsokos GC (2011) Mechanisms of disease systemic lupus erythematosus. N Engl J Med 365:2110–2121PubMed
120.
go back to reference Urbonaviciute V, Furnrohr BG, Meister S et al (2008) Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med 205:3007–3018PubMedCentralPubMed Urbonaviciute V, Furnrohr BG, Meister S et al (2008) Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med 205:3007–3018PubMedCentralPubMed
121.
go back to reference Utz PJ, Anderson P (1998) Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens. Arthritis Rheum Us 41:1152–1160 Utz PJ, Anderson P (1998) Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens. Arthritis Rheum Us 41:1152–1160
122.
123.
go back to reference Van Bavel CC, Dieker J, Muller S et al (2009) Apoptosis-associated acetylation on histone H2B is an epitope for lupus autoantibodies. Mol Immunol 47:511–516PubMed Van Bavel CC, Dieker J, Muller S et al (2009) Apoptosis-associated acetylation on histone H2B is an epitope for lupus autoantibodies. Mol Immunol 47:511–516PubMed
124.
go back to reference Van Bavel CC, Dieker JW, Kroeze Y et al (2011) Apoptosis-induced histone H3 methylation is targeted by autoantibodies in systemic lupus erythematosus. Ann Rheum Dis 70:201–207PubMed Van Bavel CC, Dieker JW, Kroeze Y et al (2011) Apoptosis-induced histone H3 methylation is targeted by autoantibodies in systemic lupus erythematosus. Ann Rheum Dis 70:201–207PubMed
125.
go back to reference Van Bavel CC, Dieker JW, Tamboer WP et al (2010) Lupus-derived monoclonal autoantibodies against apoptotic chromatin recognize acetylated conformational epitopes. Mol Immunol 48:248–256PubMed Van Bavel CC, Dieker JW, Tamboer WP et al (2010) Lupus-derived monoclonal autoantibodies against apoptotic chromatin recognize acetylated conformational epitopes. Mol Immunol 48:248–256PubMed
126.
go back to reference Van Bavel CC, Fenton KA, Rekvig OP et al (2008) Glomerular targets of nephritogenic autoantibodies in systemic lupus erythematosus. Arthritis Rheum 58:1892–1899PubMed Van Bavel CC, Fenton KA, Rekvig OP et al (2008) Glomerular targets of nephritogenic autoantibodies in systemic lupus erythematosus. Arthritis Rheum 58:1892–1899PubMed
127.
go back to reference Van Bavel CC, Van Der Vlag J, Berden JH (2007) Glomerular binding of anti-dsDNA autoantibodies: the dispute resolved? Kidney Int 71:600–601PubMed Van Bavel CC, Van Der Vlag J, Berden JH (2007) Glomerular binding of anti-dsDNA autoantibodies: the dispute resolved? Kidney Int 71:600–601PubMed
128.
go back to reference Van Bruggen MC, Kramers C, Berden JH (1996) Autoimmunity against nucleosomes and lupus nephritis. Ann Med Interne Paris 147:485–489PubMed Van Bruggen MC, Kramers C, Berden JH (1996) Autoimmunity against nucleosomes and lupus nephritis. Ann Med Interne Paris 147:485–489PubMed
129.
go back to reference Van Bruggen MC, Kramers C, Hylkema MN et al (1994) Pathophysiology of lupus nephritis: the role of nucleosomes. Neth J Med 45:273–279PubMed Van Bruggen MC, Kramers C, Hylkema MN et al (1994) Pathophysiology of lupus nephritis: the role of nucleosomes. Neth J Med 45:273–279PubMed
130.
go back to reference Van Bruggen MC, Kramers C, Hylkema MN et al (1996) Significance of anti-nuclear and anti-extracellular matrix autoantibodies for albuminuria in murine lupus nephritis; a longitudinal study on plasma and glomerular eluates in MRL/l mice. Clin Exp Immunol 105:132–139PubMed Van Bruggen MC, Kramers C, Hylkema MN et al (1996) Significance of anti-nuclear and anti-extracellular matrix autoantibodies for albuminuria in murine lupus nephritis; a longitudinal study on plasma and glomerular eluates in MRL/l mice. Clin Exp Immunol 105:132–139PubMed
131.
go back to reference Van Bruggen MC, Walgreen B, Rijke TP et al (1997) Antigen specificity of anti-nuclear antibodies complexed to nucleosomes determines glomerular basement membrane binding in vivo. Eur J Immunol 27:1564–1569PubMed Van Bruggen MC, Walgreen B, Rijke TP et al (1997) Antigen specificity of anti-nuclear antibodies complexed to nucleosomes determines glomerular basement membrane binding in vivo. Eur J Immunol 27:1564–1569PubMed
132.
go back to reference Van der Vlag J, Berden JH (2011) Lupus nephritis: role of antinucleosome autoantibodies. Semin Nephrol 31:376–389PubMed Van der Vlag J, Berden JH (2011) Lupus nephritis: role of antinucleosome autoantibodies. Semin Nephrol 31:376–389PubMed
133.
go back to reference Van Ghelue M, Moens U, Bendiksen S et al (2003) Autoimmunity to nucleosomes related to viral infection: a focus on hapten-carrier complex formation. J Autoimmun 20:171–182 Van Ghelue M, Moens U, Bendiksen S et al (2003) Autoimmunity to nucleosomes related to viral infection: a focus on hapten-carrier complex formation. J Autoimmun 20:171–182
134.
go back to reference Voll RE, Roth EA, Girkontaite I et al (1997) Histone-specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double-stranded DNA antibody production. Arthritis Rheum 40:2162–2171PubMed Voll RE, Roth EA, Girkontaite I et al (1997) Histone-specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double-stranded DNA antibody production. Arthritis Rheum 40:2162–2171PubMed
135.
go back to reference Weening JJ, D'agati VD, Schwartz MM et al (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 65:521–530PubMed Weening JJ, D'agati VD, Schwartz MM et al (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 65:521–530PubMed
136.
go back to reference Westhoff CM, Whittier A, Kathol S et al (1997) DNA-binding antibodies from viable motheaten mutant mice: implications for B cell tolerance. J Immunol 159:3024–3033PubMed Westhoff CM, Whittier A, Kathol S et al (1997) DNA-binding antibodies from viable motheaten mutant mice: implications for B cell tolerance. J Immunol 159:3024–3033PubMed
137.
go back to reference Widom J (1992) A relationship between the helical twist of DNA and the ordered positioning of nucleosomes in all eukaryotic cells. Proc Natl Acad Sci U S A 89:1095–1099PubMedCentralPubMed Widom J (1992) A relationship between the helical twist of DNA and the ordered positioning of nucleosomes in all eukaryotic cells. Proc Natl Acad Sci U S A 89:1095–1099PubMedCentralPubMed
138.
go back to reference Williams RC Jr, Malone C, Blood B et al (1999) Anti-DNA and anti-nucleosome antibody affinity—a mirror image of lupus nephritis? J Rheumatol 26:331–346PubMed Williams RC Jr, Malone C, Blood B et al (1999) Anti-DNA and anti-nucleosome antibody affinity—a mirror image of lupus nephritis? J Rheumatol 26:331–346PubMed
139.
go back to reference Winfield JB, Faiferman I, Koffler D (1977) Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. J Clin Invest 59:90–96PubMedCentralPubMed Winfield JB, Faiferman I, Koffler D (1977) Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. J Clin Invest 59:90–96PubMedCentralPubMed
140.
go back to reference Wu ZQ, Drayton D, Pisetsky DS (1997) Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 109:27–31PubMedCentralPubMed Wu ZQ, Drayton D, Pisetsky DS (1997) Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 109:27–31PubMedCentralPubMed
141.
go back to reference Xie C, Liang Z, Chang S et al (2003) Use of a novel elution regimen reveals the dominance of polyreactive antinuclear autoantibodies in lupus kidneys. Arthritis Rheum 48:2343–2352PubMed Xie C, Liang Z, Chang S et al (2003) Use of a novel elution regimen reveals the dominance of polyreactive antinuclear autoantibodies in lupus kidneys. Arthritis Rheum 48:2343–2352PubMed
142.
go back to reference Zykova SN, Seredkina N, Benjaminsen J et al (2008) Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus-prone (NZB x NZW)F(1) mice. Arthritis Rheum 58:813–825PubMed Zykova SN, Seredkina N, Benjaminsen J et al (2008) Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus-prone (NZB x NZW)F(1) mice. Arthritis Rheum 58:813–825PubMed
143.
go back to reference Zykova SN, Tveita AA, Rekvig OP (2010) Renal Dnase1 enzyme activity and protein expression is selectively shut down in murine and human membranoproliferative lupus nephritis. PLoS One 5(8):e12096 Zykova SN, Tveita AA, Rekvig OP (2010) Renal Dnase1 enzyme activity and protein expression is selectively shut down in murine and human membranoproliferative lupus nephritis. PLoS One 5(8):e12096
Metadata
Title
The pathogenesis and diagnosis of systemic lupus erythematosus: still not resolved
Authors
Ole Petter Rekvig
Johan Van der Vlag
Publication date
01-05-2014
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 3/2014
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-014-0428-6

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