KEGG   PATHWAY: hsa05332
Entry
hsa05332                    Pathway                                
Name
Graft-versus-host disease - Homo sapiens (human)
Description
Graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT) where immunocompetent donor T cells attack the genetically disparate host cells. GVHD pathophysiology can be summerized in a three-step process. Step 1 involves the development of an inflammatory milieu resulting from damage in the host tissues induced by the preparative chemotherapy or radiotherapy regimen. Damaged tissues secrete inflammatory cytokines, including interleukin 1 (IL-1), and tumor necrosis factor (TNF-alpha ). During step 2, antigen-presenting cells (APCs) trigger the activation of donor-derived T cells, which induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B.
Class
Human Diseases; Immune disease
Pathway map
hsa05332  Graft-versus-host disease
hsa05332

Disease
H00084  Graft-versus-host disease
Organism
Homo sapiens (human) [GN:hsa]
Gene
3569  IL6; interleukin 6 [KO:K05405]
3552  IL1A; interleukin 1 alpha [KO:K04383]
3553  IL1B; interleukin 1 beta [KO:K04519]
7124  TNF; tumor necrosis factor [KO:K03156]
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]
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]
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
940  CD28; CD28 molecule [KO:K06470]
3558  IL2; interleukin 2 [KO:K05429]
3105  HLA-A; major histocompatibility complex, class I, A [KO:K06751]
3106  HLA-B; major histocompatibility complex, class I, B [KO:K06751]
3107  HLA-C; major histocompatibility complex, class I, C [KO:K06751]
3134  HLA-F; major histocompatibility complex, class I, F [KO:K06751]
3135  HLA-G; major histocompatibility complex, class I, G [KO:K06751]
3133  HLA-E; major histocompatibility complex, class I, E [KO:K06751]
356  FASLG; Fas ligand [KO:K04389]
355  FAS; Fas cell surface death receptor [KO:K04390]
5551  PRF1; perforin 1 [KO:K07818]
3002  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
3458  IFNG; interferon gamma [KO:K04687]
3803  KIR2DL2; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 2 [KO:K07981]
3802  KIR2DL1; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 1 [KO:K07981]
3804  KIR2DL3; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3 [KO:K07981]
57292  KIR2DL5A; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 5A [KO:K24232]
3812  KIR3DL2; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2 [KO:K07980]
3811  KIR3DL1; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1 [KO:K07980]
115653  KIR3DL3; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 3 [KO:K07980]
3821  KLRC1; killer cell lectin like receptor C1 [KO:K06541]
3824  KLRD1; killer cell lectin like receptor D1 [KO:K06516]
Compound
C00338  Lipopolysaccharide
C00533  Nitric oxide
Reference
  Authors
Ferrara JL, Reddy P.
  Title
Pathophysiology of graft-versus-host disease.
  Journal
Semin Hematol 43:3-10 (2006)
DOI:10.1053/j.seminhematol.2005.09.001
Reference
  Authors
Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease.
  Journal
Hematol Oncol 21:149-61 (2003)
DOI:10.1002/hon.716
Reference
  Authors
Sun Y, Tawara I, Toubai T, Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease: recent advances.
  Journal
Transl Res 150:197-214 (2007)
DOI:10.1016/j.trsl.2007.06.003
Reference
  Authors
Jaksch M, Mattsson J.
  Title
The pathophysiology of acute graft-versus-host disease.
  Journal
Scand J Immunol 61:398-409 (2005)
DOI:10.1111/j.1365-3083.2005.01595.x
Reference
  Authors
Vogelsang GB, Lee L, Bensen-Kennedy DM.
  Title
Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant.
  Journal
Annu Rev Med 54:29-52 (2003)
DOI:10.1146/annurev.med.54.101601.152339
Reference
  Authors
Reddy P, Ferrara JL.
  Title
Immunobiology of acute graft-versus-host disease.
  Journal
Blood Rev 17:187-94 (2003)
DOI:10.1016/S0268-960X(03)00009-2
Reference
  Authors
Blazar BR, Murphy WJ.
  Title
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
  Journal
Philos Trans R Soc Lond B Biol Sci 360:1747-67 (2005)
DOI:10.1098/rstb.2005.1701
Reference
  Authors
Couriel D, Caldera H, Champlin R, Komanduri K.
  Title
Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management.
  Journal
Cancer 101:1936-46 (2004)
DOI:10.1002/cncr.20613
Reference
  Authors
Jacobsohn DA, Vogelsang GB.
  Title
Acute graft versus host disease.
  Journal
Orphanet J Rare Dis 2:35 (2007)
DOI:10.1186/1750-1172-2-35
Related
pathway
hsa04060  Cytokine-cytokine receptor interaction
hsa04210  Apoptosis
hsa04514  Cell adhesion molecules
hsa04612  Antigen processing and presentation
hsa04620  Toll-like receptor signaling pathway
hsa04650  Natural killer cell mediated cytotoxicity
hsa04660  T cell receptor signaling pathway
KO pathway
ko05332   

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