KEGG   PATHWAY: pcw05322
Entry
pcw05322                    Pathway                                
Name
Systemic lupus erythematosus - Phascolarctos cinereus (koala)
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
pcw05322  Systemic lupus erythematosus
pcw05322

Organism
Phascolarctos cinereus (koala) [GN:pcw]
Gene
110206037  C1QA; complement C1q subcomponent subunit A [KO:K03986]
110206039  C1QB; complement C1q subcomponent subunit B [KO:K03987]
110206038  C1QC; complement C1q subcomponent subunit C [KO:K03988]
110199442  C2; complement C2 [KO:K01332] [EC:3.4.21.43]
110199439  C4A; complement C4-A [KO:K03989]
110220185  histone H2A type 2-B [KO:K11251]
110220195  histone H2A type 2-C [KO:K11251]
110209677  histone H2A.Z [KO:K11251]
110194435  histone H2A type 1-H-like [KO:K11251]
110194439  histone H2A type 1-J [KO:K11251]
110194440  histone H2A type 3 [KO:K11251]
110194441  histone H2A type 3 [KO:K11251]
110194442  histone H2A type 1 [KO:K11251]
110194454  histone H2A type 3-like [KO:K11251]
110200089  core histone macro-H2A.2 [KO:K11251]
110207214  histone H2AX [KO:K11251]
110211741  LOW QUALITY PROTEIN: core histone macro-H2A.1 [KO:K11251]
110206559  histone H2A.V isoform X1 [KO:K11251]
110220105  histone H2A type 2-A-like isoform X1 [KO:K11251]
110220120  histone H2A type 2-A-like isoform X1 [KO:K11251]
110197514  histone H2A-beta, sperm-like [KO:K11251]
110204949  histone H2A type 2-B-like [KO:K11251]
110204194  histone H2A type 3 [KO:K11251]
110204198  histone H2A type 3 [KO:K11251]
110220165  histone H2B type 1-F/J/L-like isoform X1 [KO:K11252]
110220201  LOW QUALITY PROTEIN: histone H2B type 2-E-like [KO:K11252]
110193495  histone H2B-like [KO:K11252]
110194444  histone H2B type 1-M-like [KO:K11252]
110194446  histone H2B type 2-E [KO:K11252]
110194447  histone H2B type 2-E [KO:K11252]
110194448  histone H2B type 1-B-like [KO:K11252]
110201982  late histone H2B.L4-like [KO:K11252]
110220095  histone H2B type 2-E-like isoform X1 [KO:K11252]
110204195  histone H2B type 2-E [KO:K11252]
110204199  histone H2B type 2-E [KO:K11252]
110208673  LOW QUALITY PROTEIN: histone H2B type 2-F [KO:K11252]
110215594  histone H3.3-like [KO:K11253]
110220150  histone H3 [KO:K11253]
110194436  histone H3-like [KO:K11253]
110194443  histone H3-like isoform X1 [KO:K11253]
110219374  histone H3.3 [KO:K11253]
110205518  histone H3.3 [KO:K11253]
110206580  histone H3.3-like [KO:K11253]
110220137  histone H3 isoform X1 [KO:K11253]
110194232  uncharacterized protein LOC110194232 [KO:K11253]
110194233  LOW QUALITY PROTEIN: histone H3-like centromeric protein CSE4 [KO:K11253]
110204197  histone H3 [KO:K11253]
110220158  histone H4 [KO:K11254]
110194452  histone H4-like [KO:K11254]
110216660  uncharacterized protein LOC110216660 [KO:K11254]
110202808  uncharacterized protein LOC110202808 [KO:K11254]
110204200  histone H4 [KO:K11254]
110216652  uncharacterized protein LOC110216652 [KO:K11254]
110193709  SNRPB; small nuclear ribonucleoprotein-associated proteins B and B' isoform X1 [KO:K11086]
110197085  SNRPD1; small nuclear ribonucleoprotein Sm D1 isoform X1 [KO:K11087]
110201780  SNRPD3; small nuclear ribonucleoprotein Sm D3 [KO:K11088]
110198344  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
110218783  GRIN2B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2B [KO:K05210]
110206892  TROVE2; 60 kDa SS-A/Ro ribonucleoprotein isoform X1 [KO:K11089]
110211552  SSB; lupus La protein [KO:K11090]
110220704  ACTN1; alpha-actinin-1 isoform X1 [KO:K05699]
110202355  ACTN4; alpha-actinin-4 isoform X1 [KO:K05699]
110203296  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
110201282  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
110204537  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
110199338  rano class II histocompatibility antigen, A beta chain-like isoform X1 [KO:K06752]
110199339  HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752]
110199388  H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752]
110199389  mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
110199403  rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
110199459  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
110199460  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
110208066  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
110208102  CD86; T-lymphocyte activation antigen CD86 [KO:K05413]
110198515  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
110197721  CD40LG; CD40 ligand [KO:K03161]
110193707  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
110199397  TNF; tumor necrosis factor [KO:K03156]
110211092  IFNG; interferon gamma isoform X1 [KO:K04687]
110219537  IL10; interleukin-10 [KO:K05443]
110214297  immunoglobulin alpha-2 heavy chain-like isoform X1 [KO:K06856]
110214304  Ig heavy chain Mem5-like [KO:K06856]
110213855  C1RL; complement C1r subcomponent-like protein isoform X1 [KO:K01330] [EC:3.4.21.41]
110213817  C1R; LOW QUALITY PROTEIN: complement C1r subcomponent [KO:K01330] [EC:3.4.21.41]
110213806  C1S; complement C1s subcomponent [KO:K01331] [EC:3.4.21.42]
110197414  C3; complement C3 [KO:K03990]
110211344  C5; LOW QUALITY PROTEIN: complement C5 [KO:K03994]
110215122  C6; complement component C6 isoform X1 [KO:K03995]
110215091  C7; complement component C7 [KO:K03996]
110201329  C8A; complement component C8 alpha chain isoform X1 [KO:K03997]
110205312  C8G; complement component C8 gamma chain [KO:K03999]
110214999  C9; complement component C9 [KO:K04000]
110196241  ELANE; neutrophil elastase [KO:K01327] [EC:3.4.21.37]
110209911  low affinity immunoglobulin gamma Fc region receptor III-like isoform X1 [KO:K06472]
110209907  low affinity immunoglobulin gamma Fc region receptor III-like isoform X1 [KO:K06472]
110209910  low affinity immunoglobulin gamma Fc region receptor III-like [KO:K06463]
Compound
C00027  Hydrogen peroxide
C00434  Double-stranded DNA
C02737  Phosphatidylserine
Reference
PMID:18305268
  Authors
Rahman A, Isenberg DA.
  Title
Systemic lupus erythematosus.
  Journal
N Engl J Med 358:929-39 (2008)
DOI:10.1056/NEJMra071297
Reference
PMID:12835292
  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:17943287
  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
PMID:16932712
  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
PMID:15459673
  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
PMID:15972354
  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
PMID:10430616
  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
PMID:12965173
  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
PMID:10025913
  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
PMID:15380523
  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
pcw04060  Cytokine-cytokine receptor interaction
pcw04514  Cell adhesion molecules
pcw04610  Complement and coagulation cascades
pcw04612  Antigen processing and presentation
pcw04630  JAK-STAT signaling pathway
pcw04660  T cell receptor signaling pathway
pcw04662  B cell receptor signaling pathway
pcw04670  Leukocyte transendothelial migration
KO pathway
ko05322   
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