title: Systemic lupus erythematosus: from genes to organ damage.
abstract: Systemic lupus erythematosus (SLE) is a disease characterized by inappropriate response to self-antigens. Genetic, environmental and hormonal factors are believed to contribute to the development of the disease. We think of SLE pathogenesis as occurring in three phases of variable duration. A series of regulatory failures during the ontogeny of the immune system lead to the emergence of auto-reactive clones and the production of auto-antibodies (phase I). As the immune response to self-antigens broadens, the auto-antibody repertoire is enriched (phase II) and clinical manifestations eventually ensue (phase III). The final result is tissue damage that if not treated will lead to the functional failure of such important organs as the kidney and brain.
authors.affiliation: Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. vkyttari@bidmc.harvard.edu
authors.forename: Vasileios C
authors.initials: VC
authors.lastname: Kyttaris
mesh_terms: D017209:Apoptosis; D019411:Clinical Laboratory Techniques; D003165:Complement System Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004777:Environment; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D008297:Male; D017678:Sex Distribution
chemical_list: D016207:Cytokines; D003165:Complement System Proteins
references.citation: J Exp Med. 1998 Dec 21;188(12):2313-20
references.pmid: 9858517
references.citation: Semin Arthritis Rheum. 1996 Apr;25(5):318-36
references.pmid: 8778988
references.citation: J Immunol. 1989 Jul 1;143(1):103-12
references.pmid: 2525144
references.citation: J Exp Med. 2003 Dec 15;198(12):1863-73
references.pmid: 14662906
references.citation: J Immunol. 1983 Jun;130(6):2651-5
references.pmid: 6222112
references.citation: Arthritis Rheum. 1985 Jan;28(1):80-6
references.pmid: 3966940
references.citation: Lupus. 2008 May;17(5):426-30
references.pmid: 18490421
references.citation: Medicine (Baltimore). 2004 Jan;83(1):1-17
references.pmid: 14747764
references.citation: Rheumatology (Oxford). 2005 Aug;44(8):989-94
references.pmid: 15870153
references.citation: Autoimmun Rev. 2005 Jun;4(5):296-302
references.pmid: 15990077
references.citation: Ann Intern Med. 1995 Jul 1;123(1):42-53
references.pmid: 7762914
references.citation: Trends Immunol. 2003 May;24(5):259-63
references.pmid: 12738420
references.citation: Medicine (Baltimore). 1993 Mar;72(2):113-24
references.pmid: 8479324
references.citation: Curr Dir Autoimmun. 2004;7:87-97
references.pmid: 14719376
references.citation: J Immunol. 2005 Dec 15;175(12):8392-400
references.pmid: 16339581
references.citation: J Immunol. 2002 Nov 15;169(10):6048-55
references.pmid: 12421992
references.citation: J Exp Med. 1999 Jan 4;189(1):111-21
references.pmid: 9874568
references.citation: Arthritis Rheum. 1992 Mar;35(3):311-8
references.pmid: 1536669
references.citation: J Clin Invest. 1996 Dec 1;98(11):2549-57
references.pmid: 8958217
references.citation: Lupus. 1998;7(1):23-8
references.pmid: 9493145
references.citation: Lupus. 2002;11(12):770-3
references.pmid: 12529036
references.citation: Arthritis Rheum. 1998 May;41(5):778-99
references.pmid: 9588729
references.citation: J Exp Med. 1999 Aug 16;190(4):585-90
references.pmid: 10449529
references.citation: Clin Immunol. 2002 May;103(2):145-53
references.pmid: 12027419
references.citation: J Exp Med. 2005 Mar 7;201(5):703-11
references.pmid: 15738055
references.citation: Arthritis Rheum. 1995 Sep;38(9):1260-70
references.pmid: 7575721
references.citation: EMBO J. 1996 Sep 16;15(18):4909-18
references.pmid: 8890164
references.citation: N Engl J Med. 2005 Nov 24;353(21):2219-28
references.pmid: 16306519
references.citation: Arch Intern Med. 1990 Apr;150(4):849-53
references.pmid: 2327845
references.citation: Arthritis Rheum. 2001 May;44(5):1122-6
references.pmid: 11352244
references.citation: Arthritis Rheum. 1996 Dec;39(12):2046-51
references.pmid: 8961910
references.citation: J Immunol. 2002 May 15;168(10):5070-8
references.pmid: 11994459
references.citation: Nat Med. 2004 Apr;10(4):411-5
references.pmid: 14991050
references.citation: N Engl J Med. 2007 Sep 6;357(10):977-86
references.pmid: 17804842
references.citation: Arthritis Rheum. 1996 Apr;39(4):663-70
references.pmid: 8630118
references.citation: J Clin Invest. 1996 May 1;97(9):2063-73
references.pmid: 8621796
references.citation: Nat Genet. 2001 Aug;28(4):313-4
references.pmid: 11479590
references.citation: Arthritis Rheum. 2001 Apr;44(4):739-50
references.pmid: 11315912
references.citation: Nature. 2005 Mar 10;434(7030):243-9
references.pmid: 15665823
references.citation: Curr Opin Rheumatol. 2005 Sep;17(5):518-22
references.pmid: 16093827
references.citation: Ann Intern Med. 1995 Jun 15;122(12):940-50
references.pmid: 7755231
references.citation: Annu Rev Immunol. 2004;22:431-56
references.pmid: 15032584
references.citation: Blood. 2005 Jun 1;105(11):4390-8
references.pmid: 15701725
references.citation: Curr Opin Rheumatol. 2004 Sep;16(5):513-21
references.pmid: 15314487
references.citation: J Immunol. 2007 Feb 15;178(4):2579-88
references.pmid: 17277168
references.citation: Medicine (Baltimore). 2002 May;81(3):169-78
references.pmid: 11997714
references.citation: J Immunol. 2005 Mar 15;174(6):3518-25
references.pmid: 15749888
references.citation: Semin Arthritis Rheum. 1973;3(1):1-54
references.pmid: 4125999
references.citation: Clin Exp Rheumatol. 2004 Nov-Dec;22(6):713-21
references.pmid: 15638045
references.citation: Nat Genet. 2006 May;38(5):550-5
references.pmid: 16642019
references.citation: J Immunol. 2001 Mar 15;166(6):4216-22
references.pmid: 11238674
references.citation: Lupus. 1995 Apr;4(2):83-5
references.pmid: 7795628
references.citation: Hum Genet. 2002 Oct;111(4-5):452-5
references.pmid: 12384790
references.citation: Am J Hum Genet. 2002 Sep;71(3):543-53
references.pmid: 12145745
references.citation: J Clin Invest. 2005 Apr;115(4):996-1005
references.pmid: 15841182
references.citation: Curr Opin Rheumatol. 1999 Sep;11(5):352-6
references.pmid: 10503654
references.citation: Semin Arthritis Rheum. 2004 Oct;34(2):501-37
references.pmid: 15505768
references.citation: Am J Med. 1979 May;66(5):727-32
references.pmid: 87128
references.citation: Curr Rheumatol Rep. 2004 Oct;6(5):382-90
references.pmid: 15355751
references.citation: Hum Mol Genet. 2004 Jan 1;13(1):137-47
references.pmid: 14645206
references.citation: Arthritis Rheum. 1997 Sep;40(9):1725
references.pmid: 9324032
references.citation: Proc Natl Acad Sci U S A. 1990 Sep;87(18):7020-4
references.pmid: 2144899
references.citation: Arthritis Rheum. 2005 May;52(5):1491-503
references.pmid: 15880830
references.citation: N Engl J Med. 2008 Feb 28;358(9):900-9
references.pmid: 18204098
references.citation: Kidney Int. 2003 Apr;63(4):1475-82
references.pmid: 12631364
references.citation: J Immunol. 2007 Feb 1;178(3):1960-6
references.pmid: 17237447
references.citation: N Engl J Med. 2003 Oct 16;349(16):1526-33
references.pmid: 14561795
references.citation: J Clin Invest. 2005 Nov;115(11):3193-204
references.pmid: 16224536
references.citation: Arthritis Rheum. 2001 May;44(5):1114-21
references.pmid: 11352243
references.citation: J Clin Invest. 1998 Apr 1;101(7):1448-57
references.pmid: 9525988
references.citation: Am J Hum Genet. 2004 Sep;75(3):504-7
references.pmid: 15273934
references.citation: Eur J Immunol. 1994 Jan;24(1):191-5
references.pmid: 8020556
references.citation: Annu Rev Immunol. 2001;19:225-52
references.pmid: 11244036
references.citation: Arthritis Rheum. 1995 Nov;38(11):1713-4
references.pmid: 7488298
references.citation: Ann Rheum Dis. 1992 Nov;51(11):1197-201
references.pmid: 1466595
references.citation: Lupus. 2002;11(8):528-32
references.pmid: 12220107
references.citation: J Immunol. 2004 Jun 15;172(12):7821-31
references.pmid: 15187166
references.citation: Arthritis Rheum. 2000 Jan;43(1):120-8
references.pmid: 10643707
references.citation: J Immunol. 2007 Feb 1;178(3):1938-47
references.pmid: 17237445
references.citation: J Immunol. 2004 Sep 1;173(5):3557-63
references.pmid: 15322221
references.citation: Arthritis Rheum. 2001 Dec;44(12):2819-27
references.pmid: 11762942
references.citation: Lupus. 2002;11(11):722-9
references.pmid: 12475002
references.citation: J Exp Med. 2006 Sep 4;203(9):2157-64
references.pmid: 16923849
references.citation: Arthritis Rheum. 2002 Jun;46(6):1563-71
references.pmid: 12115187
references.citation: Arch Dermatol. 1990 Jan;126(1):52-5
references.pmid: 2404463
references.citation: J Immunol. 2002 Oct 15;169(8):4147-52
references.pmid: 12370343
references.citation: J Biol Chem. 2005 May 13;280(19):18959-66
references.pmid: 15743765
references.citation: Clin Immunol. 2001 Nov;101(2):130-5
references.pmid: 11683571
references.citation: J Immunol. 2003 Apr 15;170(8):4189-95
references.pmid: 12682251
references.citation: J Immunol. 2008 Dec 15;181(12):8761-6
references.pmid: 19050297