| H00080 | |
| H番号 | H00080 |
| 名称 | 全身性エリテマトーデス |
| 概要 | 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. |
| カテゴリ | 免疫系疾患 疾患パスウェイ hsa05322 全身性エリテマトーデス |
| ネットワーク | nt06517(H00080) TLR signaling nt06520(H00080) CGAS-STING signaling nt06530(H00080) PI3K signaling |
| 病因遺伝子 | (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] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | デキサメタゾン [DR:D00292] デキサメタゾンリン酸エステルナトリウム [DR:D00975] ベタメタゾンリン酸エステルナトリウム [DR:D00972] トリアムシノロンアセトニド [DR:D00983] アルプロスタジル [DR:D00180] ヒドロコルチゾン [DR:D00088] ヒドロコルチゾンコハク酸エステルナトリウム [DR:D00978] コルチゾン酢酸エステル [DR:D00973] トリアムシノロン [DR:D00385] ベタメタゾン [DR:D00244] プレドニゾロン [DR:D00472] プレドニゾロンコハク酸エステルナトリウム [DR:D01239] メチルプレドニゾロン [DR:D00407] メチルプレドニゾロンコハク酸エステルナトリウム [DR:D00751] メチルプレドニゾロン酢酸エステル [DR:D00979] ベリムマブ [DR:D03068] アニフロルマブ [DR:D11082] アザチオプリン [DR:D00238] ヒドロキシクロロキン硫酸塩 [DR:D02114] シクロホスファミド水和物 [DR:D00287] |
| コメント | 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] |
| リンク | ICD-11: 4A40.0 ICD-10: M32 MeSH: D008180 OMIM: 152700 601744 605218 610927 612251 612253 614420 301080 |
| 文献 | PMID:15273934 (PTPN22) 著者 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 タイトル Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. 雑誌 Am J Hum Genet 75:504-7 (2004) DOI:10.1086/423790 PMID:33331924 (FCGR2A) 著者 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 タイトル FcgammaRIIA expression accelerates nephritis and increases platelet activation in systemic lupus erythematosus. 雑誌 Blood 136:2933-2945 (2020) DOI:10.1182/blood.2020004974 PMID:15895258 (FCGR2B) 著者 Blank MC, Stefanescu RN, Masuda E, Marti F, King PD, Redecha PB, Wurzburger RJ, Peterson MG, Tanaka S, Pricop L タイトル Decreased transcription of the human FCGR2B gene mediated by the -343 G/C promoter polymorphism and association with systemic lupus erythematosus. 雑誌 Hum Genet 117:220-7 (2005) DOI:10.1007/s00439-005-1302-3 PMID:15138458 (CTLA4) 著者 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 タイトル Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. 雑誌 Eur J Hum Genet 12:620-6 (2004) DOI:10.1038/sj.ejhg.5201214 PMID:17660818 (TREX1) 著者 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 タイトル Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. 雑誌 Nat Genet 39:1065-7 (2007) DOI:10.1038/ng2091 PMID:11479590 (DNASE1) 著者 Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y タイトル Mutation of DNASE1 in people with systemic lupus erythematosus. 雑誌 Nat Genet 28:313-4 (2001) DOI:10.1038/91070 PMID:16027372 (TLR5) 著者 Hawn TR, Wu H, Grossman JM, Hahn BH, Tsao BP, Aderem A タイトル A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus. 雑誌 Proc Natl Acad Sci U S A 102:10593-7 (2005) DOI:10.1073/pnas.0501165102 PMID:12402038 (PDCD1) 著者 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 タイトル A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. 雑誌 Nat Genet 32:666-9 (2002) DOI:10.1038/ng1020 PMID:17360460 (CR2) 著者 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 タイトル Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus. 雑誌 Proc Natl Acad Sci U S A 104:3961-6 (2007) DOI:10.1073/pnas.0609101104 PMID:16642019 (IRF5) 著者 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 タイトル A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. 雑誌 Nat Genet 38:550-5 (2006) DOI:10.1038/ng1782 PMID:19109131 (STAT4) 著者 Kariuki SN, Kirou KA, MacDermott EJ, Barillas-Arias L, Crow MK, Niewold TB タイトル Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo. 雑誌 J Immunol 182:34-8 (2009) DOI:10.4049/jimmunol.182.1.34 PMID:33173951 (DNASE1L3) 著者 Zervou MI, Andreou A, Matalliotakis M, Spandidos DA, Goulielmos GN, Eliopoulos EE タイトル Association of the DNASE1L3 rs35677470 polymorphism with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis: Structural biological insights. 雑誌 Mol Med Rep 22:4492-4498 (2020) DOI:10.3892/mmr.2020.11547 PMID:35477763 (TLR7) 著者 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 タイトル TLR7 gain-of-function genetic variation causes human lupus. 雑誌 Nature 605:349-356 (2022) DOI:10.1038/s41586-022-04642-z PMID:12835292 (HLA-DRB1, HLA-DQA1, HLA-DQB1) 著者 Mok CC, Lau CS. タイトル Pathogenesis of systemic lupus erythematosus. 雑誌 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) 著者 Rahman A, Isenberg DA. タイトル Systemic lupus erythematosus. 雑誌 N Engl J Med 358:929-39 (2008) DOI:10.1056/NEJMra071297 |