KEGG   PATHWAY: rno05322
Entry
rno05322                    Pathway                                

Name
Systemic lupus erythematosus - Rattus norvegicus (rat)
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 particulary 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.
Class
Human Diseases; Immune disease
Pathway map
rno05322  Systemic lupus erythematosus
rno05322

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
298566  C1qa; complement C1q subcomponent subunit A precursor [KO:K03986]
29687  C1qb; complement C1q subcomponent subunit B precursor [KO:K03987]
362634  C1qc; complement C1q subcomponent subunit C precursor [KO:K03988]
24231  C2; complement C2 precursor [KO:K01332] [EC:3.4.21.43]
24233  C4a; complement C4 precursor [KO:K03989]
406161  C4b; complement component 4, gene 2 precursor [KO:K03989]
500987  H2ax; H2A.X variant histone [KO:K11251]
499675  H2ac20; histone H2A type 2-C [KO:K11251]
64646  Hist3h2a; histone H2A type 3 [KO:K11251]
24828  H2ac1; histone H2A type 4 [KO:K11251]
306970  Hist1h2an; histone cluster 1, H2an [KO:K11251]
498753  Hist1h2af; histone H2a [KO:K11251]
502125  Hist1h2ah; histone H2A type 1-E [KO:K11251]
502129  hist1h2ail2; histone H2A type 1-B [KO:K11251]
680615  Hist1h2ak; histone cluster 1, H2ak [KO:K11251]
690102  H2ac21; H2A clustered histone 21 [KO:K11251]
690131  Hist2h2aa2; histone H2A type 2-A [KO:K11251]
690795  H2aj; histone H2A.J [KO:K11251]
306962  Hist1h2ac; histone H2A type 1-B [KO:K11251]
29384  Macroh2a1; core histone macro-H2A.1 [KO:K11251]
361844  Macroh2a2; core histone macro-H2A.2 [KO:K11251]
498894  RGD1560813; histone H2A.V-like [KO:K11251]
685069  histone H2A.V-like [KO:K11251]
685909  H2az2; H2A.Z variant histone 2 [KO:K11251]
689408  histone H2A.V-like [KO:K11251]
365877  Hist2h2aa3; histone H2A type 1 [KO:K11251]
58940  H2az1; histone H2A.Z [KO:K11251]
680322  H2ac12; histone H2A type 1-H [KO:K11251]
302783  H2ab3; H2A.B variant histone 3 [KO:K11251]
100360754  Hist1h2ai; histone H2A type 1-B [KO:K11251]
100363171  histone H2A-Bbd type 1 [KO:K11251]
100910554  histone H2A type 1-B-like [KO:K11251]
103690190  histone H2A type 1-E [KO:K11251]
684773  histone H2A type 1-B [KO:K11251]
291157  Hist1h2bo; histone cluster 1 H2B family member o [KO:K11252]
24829  H2bc1; histone H2B type 1-A [KO:K11252]
684444  histone H2B subacrosomal variant [KO:K11252]
306945  Hist1h2bq; histone cluster 1 H2B family member Q [KO:K11252]
306969  Hist1h2bl; histone H2B type 1-C/E/F/G/I [KO:K11252]
295274  Hist2h2be; histone H2B type 2-E [KO:K11252]
303175  Hist3h2ba; histone cluster 3, H2ba [KO:K11252]
361247  Hist1h2bd; histone cluster 1 H2B family member D [KO:K11252]
64647  Hist1h2bg; histone H2B type 1 [KO:K11252]
680403  Hist1h2bc; histone H2B type 1-C/E/F/G/I [KO:K11252]
684797  histone H2B type 1-C/E/F/G/I [KO:K11252]
691488  H2bu1; H2B.U histone 1 [KO:K11252]
680312  H2bc12; histone H2B [KO:K11252]
100364835  histone H2B type 1-C/E/F/G/I [KO:K11252]
100365043  histone H2B type 1-C/E/F/G/I [KO:K11252]
100910200  histone H2B type 1-C/E/F/G/I [KO:K11252]
100912338  histone H2B type 2-F [KO:K11252]
102549061  histone H2B type 1-B [KO:K11252]
103690887  histone H2B-like [KO:K11252]
100359692  H2bc9; histone H2B type 1-C/E/F/G/I [KO:K11252]
691496  H3f4; H3.4 histone [KO:K11253]
367254  RGD1564447; histone H3.3A-like [KO:K11253]
291159  Hist1h2ail1; histone H3.1 [KO:K11253]
117056  H3f3b; histone H3.3 [KO:K11253]
310678  Hist2h3c2; histone cluster 2 H3 family member C2 [KO:K11253]
679994  H3c1; histone H3.1 [KO:K11253]
680498  Hist1h3b; histone H3.1 [KO:K11253]
684762  H3c13; histone H3 [KO:K11253]
500882  RGD1564548; histone H3.3A-like [KO:K11253]
100361558  H3f3a; histone H3.3A [KO:K11253]
102551184  uncharacterized protein LOC102551184 [KO:K11253]
102549173  LOW QUALITY PROTEIN: uncharacterized protein LOC102549173 [KO:K11253]
102548682  uncharacterized protein LOC102548682 [KO:K11253]
100360868  H3f3c; histone H3.3A [KO:K11253]
100360950  histone H3.1 [KO:K11253]
100359421  histone H3.3A-like [KO:K11253]
108349691  histone H3.3A-like [KO:K11253]
295277  Hist2h4; histone H4 [KO:K11254]
64627  Hist1h4b; histone H4 [KO:K11254]
291152  Hist1h4m; histone H4 [KO:K11254]
364723  Hist1h2ao; histone H2A type 1-E [KO:K11254]
171365  Snrpb; small nuclear ribonucleoprotein-associated protein B [KO:K11086]
291794  Snrpd1; small nuclear ribonucleoprotein Sm D1 [KO:K11087]
687711  Snrpd3; small nuclear ribonucleoprotein Sm D3 [KO:K11088]
24409  Grin2a; glutamate receptor ionotropic, NMDA 2A precursor [KO:K05209]
24410  Grin2b; glutamate receptor ionotropic, NMDA 2B precursor [KO:K05210]
308901  Trim21; E3 ubiquitin-protein ligase TRIM21 [KO:K10651] [EC:2.3.2.27]
304833  Ro60; 60 kDa SS-A/Ro ribonucleoprotein [KO:K11089]
81783  Ssb; lupus La protein homolog [KO:K11090]
63836  Actn4; alpha-actinin-4 [KO:K05699]
81634  Actn1; alpha-actinin-1 [KO:K05699]
294274  RT1-DMa; RT1 class II, DM alpha precursor [KO:K06752]
294273  RT1-DMb; RT1 class II, DM beta precursor [KO:K06752]
24984  RT1-DOa; RT1 class II, locus DOa precursor [KO:K06752]
24986  RT1-Ha; RT1 class II, locus Ha precursor [KO:K06752]
294269  RT1-Da; RT1 class II, locus Da precursor [KO:K06752]
294270  RT1-Db1; rano class II histocompatibility antigen, D-1 beta chain precursor [KO:K06752]
309621  RT1-Ba; rano class II histocompatibility antigen, B alpha chain precursor [KO:K06752]
309622  RT1-Bb; rano class II histocompatibility antigen, B-1 beta chain precursor [KO:K06752]
365542  RT1-DOb; RT1 class II, DO beta [KO:K06752]
24981  RT1-Db2; RT1 class II, locus Db2 precursor [KO:K06752]
25408  Cd80; T-lymphocyte activation antigen CD80 [KO:K05412]
56822  Cd86; T-lymphocyte activation antigen CD86 precursor [KO:K05413]
25660  Cd28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470]
84349  Cd40lg; CD40 ligand [KO:K03161]
171369  Cd40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]
24835  Tnf; tumor necrosis factor [KO:K03156]
25712  Ifng; interferon gamma precursor [KO:K04687]
25325  Il10; interleukin-10 precursor [KO:K05443]
312705  C1r; complement C1r subcomponent precursor [KO:K01330] [EC:3.4.21.41]
192262  C1s; complement C1s subcomponent precursor [KO:K01331] [EC:3.4.21.42]
24232  C3; complement C3 precursor [KO:K03990]
362119  C5; complement C5 precursor [KO:K03994]
24237  C6; complement component C6 precursor [KO:K03995]
117517  C7; LOW QUALITY PROTEIN: complement component C7 [KO:K03996]
298288  C8a; complement component C8 alpha chain precursor [KO:K03997]
313421  C8b; complement component C8 beta chain precursor [KO:K03998]
296545  C8g; complement component C8 gamma chain [KO:K03999]
117512  C9; complement component C9 [KO:K04000]
290257  Ctsg; cathepsin G precursor [KO:K01319] [EC:3.4.21.20]
299606  Elane; neutrophil elastase precursor [KO:K01327] [EC:3.4.21.37]
295279  Fcgr1a; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498]
498276  Fc gamma receptor II beta [KO:K06472]
116591  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor III [KO:K06463]
304966  Fcgr3a; Fc fragment of IgG receptor IIIa precursor [KO:K06463]
Compound
C00027  Hydrogen peroxide
C00434  Double-stranded DNA
C02737  Phosphatidylserine
Reference
  Authors
Rahman A, Isenberg DA.
  Title
Systemic lupus erythematosus.
  Journal
N Engl J Med 358:929-39 (2008)
DOI:10.1056/NEJMra071297
Reference
  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
  Authors
Clatworthy MR, Smith KG.
  Title
B cells in glomerulonephritis: focus on lupus nephritis.
  Journal
Semin Immunopathol 29:337-53 (2007)
DOI:10.1007/s00281-007-0092-1
Reference
PMID:8048228
  Authors
Couser WG.
  Title
New insights into mechanisms of immune glomerular injury.
  Journal
West J Med 160:440-6 (1994)
Reference
  Authors
Cook HT, Botto M.
  Title
Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus.
  Journal
Nat Clin Pract Rheumatol 2:330-7 (2006)
DOI:10.1038/ncprheum0191
Reference
  Authors
Carroll MC.
  Title
A protective role for innate immunity in systemic lupus erythematosus.
  Journal
Nat Rev Immunol 4:825-31 (2004)
DOI:10.1038/nri1456
Reference
  Authors
Sturfelt G, Truedsson L.
  Title
Complement and its breakdown products in SLE.
  Journal
Rheumatology (Oxford) 44:1227-32 (2005)
DOI:10.1093/rheumatology/keh719
Reference
  Authors
Lu L, Kaliyaperumal A, Boumpas DT, Datta SK.
  Title
Major peptide autoepitopes for nucleosome-specific T cells of human lupus.
  Journal
J Clin Invest 104:345-55 (1999)
DOI:10.1172/JCI6801
Reference
  Authors
Zieve GW, Khusial PR.
  Title
The anti-Sm immune response in autoimmunity and cell biology.
  Journal
Autoimmun Rev 2:235-40 (2003)
DOI:10.1016/S1568-9972(03)00018-1
Reference
  Authors
Scofield RH, Farris AD, Horsfall AC, Harley JB.
  Title
Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins.
  Journal
Arthritis Rheum 42:199-209 (1999)
DOI:10.1002/1529-0131(199902)42:2<199::AID-ANR1>3.0.CO;2-1
Reference
  Authors
Hoffman RW.
  Title
T cells in the pathogenesis of systemic lupus erythematosus.
  Journal
Clin Immunol 113:4-13 (2004)
DOI:10.1016/j.clim.2004.05.001
Related
pathway
rno04060  Cytokine-cytokine receptor interaction
rno04514  Cell adhesion molecules
rno04610  Complement and coagulation cascades
rno04612  Antigen processing and presentation
rno04630  JAK-STAT signaling pathway
rno04660  T cell receptor signaling pathway
rno04662  B cell receptor signaling pathway
rno04670  Leukocyte transendothelial migration
KO pathway
ko05322   

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