KEGG   DISEASE: Systemic lupus erythematosus
Entry
H00080                      Disease                                
Name
Systemic lupus erythematosus
Description
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and certain cytoplasmic components, in association with a diverse array of clinical manifestations. The primary pathological findings in patients with SLE are those of inflammation, vasculitis, immune complex deposition, and vasculopathy. Immune complexes comprising autoantibody and self-antigen is deposited particularly in the renal glomeruli and mediate a systemic inflammatory response by activating complement or via Fc{gamma}R-mediated neutrophil and macrophage activation. Activation of complement (C5) leads to injury both through formation of the membrane attack complex (C5b-9) or by generation of the anaphylatoxin and cell activator C5a. Neutrophils and macrophages cause tissue injury by the release of oxidants and proteases. It has been reported that there is a relatively high genetic component behind SLE. The data of family-based studies point toward an oligogenic background, with several susceptibility genes (SLEB) acting on disease expression along with environmental factors.
Category
Immune system disease
Brite
Human diseases [BR:br08402]
 Immune system diseases
  Allergies and autoimmune diseases
   H00080  Systemic lupus erythematosus
Human diseases in ICD-11 classification [BR:br08403]
 04 Diseases of the immune system
  Nonorgan specific systemic autoimmune disorders
   4A40  Lupus erythematosus
    H00080  Systemic lupus erythematosus
Pathway
hsa05322  Systemic lupus erythematosus
Related
pathway
hsa04145 Phagosome   
hsa04640 Hematopoietic cell lineage   
hsa04666 Fc gamma R-mediated phagocytosis   
Gene
(SLE) PTPN22 [HSA:26191] [KO:K18024]
(SLE) FCGR2A [HSA:2212] [KO:K06472]
(SLE) FCGR2B [HSA:2213] [KO:K12560]
(SLE) CTLA4 [HSA:1493] [KO:K06538]
(SLE) TREX1 [HSA:11277] [KO:K10790]
(SLE) DNASE1 [HSA:1773] [KO:K11994]
(SLEB1) TLR5 [HSA:7100] [KO:K10168]
(SLEB2) PDCD1 [HSA:5133] [KO:K06744]
(SLEB9) CR2 [HSA:1380] [KO:K04012]
(SLEB10) IRF5 [HSA:3663] [KO:K09446]
(SLEB11) STAT4 [HSA:6775] [KO:K11222]
(SLEB16) DNASE1L3 [HSA:1776] [KO:K11995]
HLA-DRB1 [HSA:3123] [KO:K06752]
HLA-DQA1 [HSA:3117] [KO:K06752]
HLA-DQB1 [HSA:3119] [KO:K06752]
C2 [HSA:717] [KO:K01332]
C4A [HSA:720] [KO:K03989]
TNF [HSA:7124] [KO:K03156]
FCGR3A [HSA:2214] [KO:K06463]
FCGR3B [HSA:2215] [KO:K06463]
CRP [HSA:1401] [KO:K16143]
ZNF423 [HSA:23090] [KO:K22870]
Env factor
Hydrazines
Procainamide
Chlorpromazine [CPD:C06906 C07952]
Isoniazid [CPD:C07054]
Phenytoin [CPD:C07443]
Penicillamine [CPD:C07418]
Tobacco smoke
Hair dyes
Ultraviolet light
Drug
Triamcinolone acetonide [DR:D00983]
Dexamethasone [DR:D00292]
Dexamethasone sodium phosphate [DR:D00975]
Hydrocortisone [DR:D00088]
Hydrocortisone sodium succinate [DR:D00978]
Prednisolone [DR:D00472]
Prednisolone sodium phosphate [DR:D00981]
Prednisone [DR:D00473]
Methylprednisolone [DR:D00407]
Methylprednisolone sodium succinate [DR:D00751]
Methylprednisolone acetate [DR:D00979]
Corticotropin [DR:D00146]
Cortisone acetate [DR:D00973]
Belimumab [DR:D03068]
Anifrolumab [DR:D11082]
Hydroxychloroquine sulfate [DR:D02114]
Comment
Autoantigen:
Double-stranded DNA [CPD:C00434]
H2A [HSA:474382]
H2B [HSA:8346]
H3 [HSA:3020]
H4 [HSA:8359]
Ro/SS-A [HSA:6737]
La/SS-B [HSA:6741]
Sm-B [HSA:6628]
Sm-D [HSA:6632]
NR2A [HSA:2903]
NR2B [HSA:2904]
Phosphatidyl-serine [CPD:C02737]
C1q [HSA:712]
Other DBs
ICD-11: 4A40.0
ICD-10: M32
MeSH: D008180
OMIM: 152700 601744 605218 610927 612251 612253 614420
Reference
PMID:15273934 (PTPN22)
  Authors
Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW
  Title
Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.
  Journal
Am J Hum Genet 75:504-7 (2004)
DOI:10.1086/423790
Reference
PMID:33331924 (FCGR2A)
  Authors
Melki I, Allaeys I, Tessandier N, Mailhot B, Cloutier N, Campbell RA, Rowley JW, Salem D, Zufferey A, Laroche A, Levesque T, Patey N, Rauch J, Lood C, Droit A, McKenzie SE, Machlus KR, Rondina MT, Lacroix S, Fortin PR, Boilard E
  Title
FcgammaRIIA expression accelerates nephritis and increases platelet activation in systemic lupus erythematosus.
  Journal
Blood 136:2933-2945 (2020)
DOI:10.1182/blood.2020004974
Reference
PMID:15895258 (FCGR2B)
  Authors
Blank MC, Stefanescu RN, Masuda E, Marti F, King PD, Redecha PB, Wurzburger RJ, Peterson MG, Tanaka S, Pricop L
  Title
Decreased transcription of the human FCGR2B gene mediated by the -343 G/C promoter polymorphism and association with systemic lupus erythematosus.
  Journal
Hum Genet 117:220-7 (2005)
DOI:10.1007/s00439-005-1302-3
Reference
PMID:15138458 (CTLA4)
  Authors
Barreto M, Santos E, Ferreira R, Fesel C, Fontes MF, Pereira C, Martins B, Andreia R, Viana JF, Crespo F, Vasconcelos C, Ferreira C, Vicente AM
  Title
Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus.
  Journal
Eur J Hum Genet 12:620-6 (2004)
DOI:10.1038/sj.ejhg.5201214
Reference
PMID:17660818 (TREX1)
  Authors
Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, de Silva U, Bailey SL, Witte T, Vyse TJ, Kere J, Pfeiffer C, Harvey S, Wong A, Koskenmies S, Hummel O, Rohde K, Schmidt RE, Dominiczak AF, Gahr M, Hollis T, Perrino FW, Lieberman J, Hubner N
  Title
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus.
  Journal
Nat Genet 39:1065-7 (2007)
DOI:10.1038/ng2091
Reference
PMID:11479590 (DNASE1)
  Authors
Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y
  Title
Mutation of DNASE1 in people with systemic lupus erythematosus.
  Journal
Nat Genet 28:313-4 (2001)
DOI:10.1038/91070
Reference
PMID:16027372 (TLR5)
  Authors
Hawn TR, Wu H, Grossman JM, Hahn BH, Tsao BP, Aderem A
  Title
A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus.
  Journal
Proc Natl Acad Sci U S A 102:10593-7 (2005)
DOI:10.1073/pnas.0501165102
Reference
PMID:12402038 (PDCD1)
  Authors
Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdottir H, Grondal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jonssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcon-Segovia D, Steinsson K, Alarcon-Riquelme ME
  Title
A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.
  Journal
Nat Genet 32:666-9 (2002)
DOI:10.1038/ng1020
Reference
PMID:17360460 (CR2)
  Authors
Wu H, Boackle SA, Hanvivadhanakul P, Ulgiati D, Grossman JM, Lee Y, Shen N, Abraham LJ, Mercer TR, Park E, Hebert LA, Rovin BH, Birmingham DJ, Chang DM, Chen CJ, McCurdy D, Badsha HM, Thong BY, Chng HH, Arnett FC, Wallace DJ, Yu CY, Hahn BH, Cantor RM, Tsao BP
  Title
Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus.
  Journal
Proc Natl Acad Sci U S A 104:3961-6 (2007)
DOI:10.1073/pnas.0609101104
Reference
PMID:16642019 (IRF5)
  Authors
Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, Gonzalez Escribano MF, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martin J, Altshuler D, Behrens TW, Alarcon-Riquelme ME
  Title
A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus.
  Journal
Nat Genet 38:550-5 (2006)
DOI:10.1038/ng1782
Reference
PMID:19109131 (STAT4)
  Authors
Kariuki SN, Kirou KA, MacDermott EJ, Barillas-Arias L, Crow MK, Niewold TB
  Title
Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo.
  Journal
J Immunol 182:34-8 (2009)
DOI:10.4049/jimmunol.182.1.34
Reference
PMID:33173951 (DNASE1L3)
  Authors
Zervou MI, Andreou A, Matalliotakis M, Spandidos DA, Goulielmos GN, Eliopoulos EE
  Title
Association of the DNASE1L3 rs35677470 polymorphism with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis: Structural biological insights.
  Journal
Mol Med Rep 22:4492-4498 (2020)
DOI:10.3892/mmr.2020.11547
Reference
PMID:12835292 (HLA-DRB1, HLA-DQA1, HLA-DQB1)
  Authors
Mok CC, Lau CS.
  Title
Pathogenesis of systemic lupus erythematosus.
  Journal
J Clin Pathol 56:481-90 (2003)
DOI:10.1136/jcp.56.7.481
Reference
PMID:18305268 (HLA-DRB1, C2, C4A, TNF, FCGR3A, FCGR3B, CRP, ZNF423)
  Authors
Rahman A, Isenberg DA.
  Title
Systemic lupus erythematosus.
  Journal
N Engl J Med 358:929-39 (2008)
DOI:10.1056/NEJMra071297
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