KEGG   PATHWAY: hsa05322
Entry
hsa05322                    Pathway                                
Name
Systemic lupus erythematosus - Homo sapiens (human)
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
hsa05322  Systemic lupus erythematosus
hsa05322

Disease
H00080  Systemic lupus erythematosus
Organism
Homo sapiens (human) [GN:hsa]
Gene
100293534  C4B_2; complement component 4B (Chido/Rodgers blood group), copy 2 [KO:K03989]
102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
102724334  [KO:K11252]
110384692  [KO:K03989]
114483833  H2BK1; H2B.K variant histone 1 [KO:K11252]
115482686  H2AL3; H2A.L variant histone 3 [KO:K11251]
121504  H4C16; H4 histone 16 [KO:K11254]
124905743  FCGR3B; low affinity immunoglobulin gamma Fc region receptor III-B [KO:K06463]
126961  H3C14; H3 clustered histone 14 [KO:K11253]
128312  H2BC26; H2B clustered histone 26 [KO:K11252]
1511  CTSG; cathepsin G [KO:K01319] [EC:3.4.21.20]
158983  H2BW1; H2B.W histone 1 [KO:K11252]
1991  ELANE; elastase, neutrophil expressed [KO:K01327] [EC:3.4.21.37]
2209  FCGR1A; Fc gamma receptor Ia [KO:K06498]
2212  FCGR2A; Fc gamma receptor IIa [KO:K06472]
2214  FCGR3A; Fc gamma receptor IIIa [KO:K06463]
2215  FCGR3B; Fc gamma receptor IIIb [KO:K06463]
221613  H2AC1; H2A clustered histone 1 [KO:K11251]
255626  H2BC1; H2B clustered histone 1 [KO:K11252]
286436  H2BW2; H2B.W histone 2 [KO:K11252]
2903  GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209]
2904  GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210]
3012  H2AC8; H2A clustered histone 8 [KO:K11251]
3013  H2AC7; H2A clustered histone 7 [KO:K11251]
3014  H2AX; H2A.X variant histone [KO:K11251]
3015  H2AZ1; H2A.Z variant histone 1 [KO:K11251]
3017  H2BC5; H2B clustered histone 5 [KO:K11252]
3018  H2BC3; H2B clustered histone 3 [KO:K11252]
3020  H3-3A; H3.3 histone A [KO:K11253]
3021  H3-3B; H3.3 histone B [KO:K11253]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3120  HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
317772  H2AC21; H2A clustered histone 21 [KO:K11251]
333932  H3C15; H3 clustered histone 15 [KO:K11253]
3458  IFNG; interferon gamma [KO:K04687]
3586  IL10; interleukin 10 [KO:K05443]
440093  H3-5; H3.5 histone [KO:K11253]
440689  H2BC18; H2B clustered histone 18 [KO:K11252]
474381  H2AB2; H2A.B variant histone 2 [KO:K11251]
474382  H2AB1; H2A.B variant histone 1 [KO:K11251]
54145  H2BC12L; H2B clustered histone 12 like [KO:K11252]
554313  H4C15; H4 clustered histone 15 [KO:K11254]
55506  MACROH2A2; macroH2A.2 histone [KO:K11251]
55766  H2AJ; H2A.J histone [KO:K11251]
653604  H3C13; H3 clustered histone 13 [KO:K11253]
6628  SNRPB; small nuclear ribonucleoprotein polypeptides B and B1 [KO:K11086]
6632  SNRPD1; small nuclear ribonucleoprotein D1 polypeptide [KO:K11087]
6634  SNRPD3; small nuclear ribonucleoprotein D3 polypeptide [KO:K11088]
6737  TRIM21; tripartite motif containing 21 [KO:K10651] [EC:2.3.2.27]
6738  RO60; Ro60, Y RNA binding protein [KO:K11089]
6741  SSB; small RNA binding exonuclease protection factor La [KO:K11090]
712  C1QA; complement C1q A chain [KO:K03986]
7124  TNF; tumor necrosis factor [KO:K03156]
713  C1QB; complement C1q B chain [KO:K03987]
714  C1QC; complement C1q C chain [KO:K03988]
715  C1R; complement C1r [KO:K01330] [EC:3.4.21.41]
716  C1S; complement C1s [KO:K01331] [EC:3.4.21.42]
717  C2; complement C2 [KO:K01332] [EC:3.4.21.43]
718  C3; complement C3 [KO:K03990]
720  C4A; complement C4A (Chido/Rodgers blood group) [KO:K03989]
721  C4B; complement C4B (Chido/Rodgers blood group) [KO:K03989]
723790  H2AC19; H2A clustered histone 19 [KO:K11251]
727  C5; complement C5 [KO:K03994]
729  C6; complement C6 [KO:K03995]
730  C7; complement C7 [KO:K03996]
731  C8A; complement C8 alpha chain [KO:K03997]
732  C8B; complement C8 beta chain [KO:K03998]
733  C8G; complement C8 gamma chain [KO:K03999]
735  C9; complement C9 [KO:K04000]
81  ACTN4; actinin alpha 4 [KO:K05699]
8290  H3-4; H3.4 histone, cluster member [KO:K11253]
8294  H4C9; H4 clustered histone 9 [KO:K11254]
8329  H2AC13; H2A clustered histone 13 [KO:K11251]
8330  H2AC15; H2A clustered histone 15 [KO:K11251]
8331  H2AC14; H2A clustered histone 14 [KO:K11251]
8332  H2AC16; H2A clustered histone 16 [KO:K11251]
8334  H2AC6; H2A clustered histone 6 [KO:K11251]
8335  H2AC4; H2A clustered histone 4 [KO:K11251]
8336  H2AC17; H2A clustered histone 17 [KO:K11251]
8337  H2AC18; H2A clustered histone 18 [KO:K11251]
8338  H2AC20; H2A clustered histone 20 [KO:K11251]
8339  H2BC8; H2B clustered histone 8 [KO:K11252]
8340  H2BC13; H2B clustered histone 13 [KO:K11252]
8341  H2BC15; H2B clustered histone 15 [KO:K11252]
8342  H2BC14; H2B clustered histone 14 [KO:K11252]
8343  H2BC7; H2B clustered histone 7 [KO:K11252]
8344  H2BC6; H2B clustered histone 6 [KO:K11252]
8345  H2BC9; H2B clustered histone 9 [KO:K11252]
8346  H2BC10; H2B clustered histone 10 [KO:K11252]
8347  H2BC4; H2B clustered histone 4 [KO:K11252]
8348  H2BC17; H2B clustered histone 17 [KO:K11252]
8349  H2BC21; H2B clustered histone 21 [KO:K11252]
8350  H3C1; H3 clustered histone 1 [KO:K11253]
8351  H3C4; H3 clustered histone 4 [KO:K11253]
8352  H3C3; H3 clustered histone 3 [KO:K11253]
8353  H3C6; H3 clustered histone 6 [KO:K11253]
8354  H3C11; H3 clustered histone 11 [KO:K11253]
8355  H3C8; H3 clustered histone 8 [KO:K11253]
8356  H3C12; H3 clustered histone 12 [KO:K11253]
8357  H3C10; H3 clustered histone 10 [KO:K11253]
8358  H3C2; H3 clustered histone 2 [KO:K11253]
8359  H4C1; H4 clustered histone 1 [KO:K11254]
8360  H4C4; H4 clustered histone 4 [KO:K11254]
8361  H4C6; H4 clustered histone 6 [KO:K11254]
8362  H4C12; H4 clustered histone 12 [KO:K11254]
8363  H4C11; H4 clustered histone 11 [KO:K11254]
8364  H4C3; H4 clustered histone 3 [KO:K11254]
8365  H4C8; H4 clustered histone 8 [KO:K11254]
8366  H4C2; H4 clustered histone 2 [KO:K11254]
8367  H4C5; H4 clustered histone 5 [KO:K11254]
8368  H4C13; H4 clustered histone 13 [KO:K11254]
8369  H4C7; H4 clustered histone 7 [KO:K11254]
8370  H4C14; H4 clustered histone 14 [KO:K11254]
83740  H2AB3; H2A.B variant histone 3 [KO:K11251]
85235  H2AC12; H2A clustered histone 12 [KO:K11251]
85236  H2BC12; H2B clustered histone 12 [KO:K11252]
87  ACTN1; actinin alpha 1 [KO:K05699]
8968  H3C7; H3 clustered histone 7 [KO:K11253]
8969  H2AC11; H2A clustered histone 11 [KO:K11251]
8970  H2BC11; H2B clustered histone 11 [KO:K11252]
92815  H2AC25; H2A clustered histone 25 [KO:K11251]
940  CD28; CD28 molecule [KO:K06470]
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
94239  H2AZ2; H2A.Z variant histone 2 [KO:K11251]
9555  MACROH2A1; macroH2A.1 histone [KO:K11251]
958  CD40; CD40 molecule [KO:K03160]
959  CD40LG; CD40 ligand [KO:K03161]
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
hsa04060  Cytokine-cytokine receptor interaction
hsa04514  Cell adhesion molecules
hsa04610  Complement and coagulation cascades
hsa04612  Antigen processing and presentation
hsa04630  JAK-STAT signaling pathway
hsa04660  T cell receptor signaling pathway
hsa04662  B cell receptor signaling pathway
hsa04670  Leukocyte transendothelial migration
KO pathway
ko05322   

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