KEGG   DISEASE: 全身性エリテマトーデス
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.
ICD-11 による疾患分類 [BR:jp08403]
 04 免疫系の疾患
   4A40  エリテマトーデス [紅斑性狼瘡]
    H00080  全身性エリテマトーデス
パスウェイに基づく疾患分類 [BR:jp08402]
  nt06517  TLR シグナリング
   H00080  全身性エリテマトーデス
  nt06520  CGAS-STING シグナリング
   H00080  全身性エリテマトーデス
  nt06537  TCR/BCR シグナリング
   H00080  全身性エリテマトーデス
指定難病 [jp08407.html]
hsa05322  全身性エリテマトーデス
hsa04620 Toll-like receptor signaling pathway   
hsa04623 Cytosolic DNA-sensing pathway   
hsa04660 T cell receptor signaling pathway   
nt06517 TLR signaling
nt06520 CGAS-STING signaling
nt06537 TCR/BCR signaling
(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]
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]
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]
ICD-11: 4A40.0
ICD-10: M32
MeSH: D008180
OMIM: 152700 601744 605218 610927 612251 612253 614420 301080
PMID:15273934 (PTPN22)
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
Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.
Am J Hum Genet 75:504-7 (2004)
PMID:33331924 (FCGR2A)
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
FcgammaRIIA expression accelerates nephritis and increases platelet activation in systemic lupus erythematosus.
Blood 136:2933-2945 (2020)
PMID:15895258 (FCGR2B)
Blank MC, Stefanescu RN, Masuda E, Marti F, King PD, Redecha PB, Wurzburger RJ, Peterson MG, Tanaka S, Pricop L
Decreased transcription of the human FCGR2B gene mediated by the -343 G/C promoter polymorphism and association with systemic lupus erythematosus.
Hum Genet 117:220-7 (2005)
PMID:15138458 (CTLA4)
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
Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus.
Eur J Hum Genet 12:620-6 (2004)
PMID:17660818 (TREX1)
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
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus.
Nat Genet 39:1065-7 (2007)
PMID:11479590 (DNASE1)
Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y
Mutation of DNASE1 in people with systemic lupus erythematosus.
Nat Genet 28:313-4 (2001)
PMID:16027372 (TLR5)
Hawn TR, Wu H, Grossman JM, Hahn BH, Tsao BP, Aderem A
A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus.
Proc Natl Acad Sci U S A 102:10593-7 (2005)
PMID:12402038 (PDCD1)
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
A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.
Nat Genet 32:666-9 (2002)
PMID:17360460 (CR2)
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
Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus.
Proc Natl Acad Sci U S A 104:3961-6 (2007)
PMID:16642019 (IRF5)
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
A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus.
Nat Genet 38:550-5 (2006)
PMID:19109131 (STAT4)
Kariuki SN, Kirou KA, MacDermott EJ, Barillas-Arias L, Crow MK, Niewold TB
Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo.
J Immunol 182:34-8 (2009)
PMID:33173951 (DNASE1L3)
Zervou MI, Andreou A, Matalliotakis M, Spandidos DA, Goulielmos GN, Eliopoulos EE
Association of the DNASE1L3 rs35677470 polymorphism with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis: Structural biological insights.
Mol Med Rep 22:4492-4498 (2020)
PMID:35477763 (TLR7)
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
TLR7 gain-of-function genetic variation causes human lupus.
Nature 605:349-356 (2022)
PMID:12835292 (HLA-DRB1, HLA-DQA1, HLA-DQB1)
Mok CC, Lau CS.
Pathogenesis of systemic lupus erythematosus.
J Clin Pathol 56:481-90 (2003)
PMID:18305268 (HLA-DRB1, C2, C4A, TNF, FCGR3A, FCGR3B, CRP, ZNF423)
Rahman A, Isenberg DA.
Systemic lupus erythematosus.
N Engl J Med 358:929-39 (2008)

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