| H00080 | |
| H number | H00080 |
| 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 DIS_PATHWAY hsa05322 Systemic lupus erythematosus |
| Network | nt06517(H00080) TLR signaling nt06520(H00080) CGAS-STING signaling nt06530(H00080) PI3K signaling |
| 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] (SLEB17) TLR7 [HSA:51284] [KO:K05404] 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] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| 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 301080 |
| 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 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 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 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 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 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 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 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 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 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 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 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 PMID:35477763 (TLR7) AUTHORS Brown GJ, Canete PF, Wang H, Medhavy A, Bones J, Roco JA, He Y, Qin Y, Cappello J, Ellyard JI, Bassett K, Shen Q, Burgio G, Zhang Y, Turnbull C, Meng X, Wu P, Cho E, Miosge LA, Andrews TD, Field MA, Tvorogov D, Lopez AF, Babon JJ, Lopez CA, Gonzalez-Murillo A, Garulo DC, Pascual V, Levy T, Mallack EJ, Calame DG, Lotze T, Lupski JR, Ding H, Ullah TR, Walters GD, Koina ME, Cook MC, Shen N, de Lucas Collantes C, Corry B, Gantier MP, Athanasopoulos V, Vinuesa CG TITLE TLR7 gain-of-function genetic variation causes human lupus. JOURNAL Nature 605:349-356 (2022) DOI:10.1038/s41586-022-04642-z 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 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 |