PATHWAY: hsa05332 Help
Entry 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 diseaseBRITE hierarchy
Pathway map Ortholog table Disease H00084 Graft-versus-host disease
Organism Homo sapiens (human) [GN:
hsa ]
Gene 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 ]
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 ]
355 FAS; Fas cell surface death receptor [KO:K04390 ]
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 ]
3813 KIR3DS1; killer cell immunoglobulin like receptor, three Ig domains and short cytoplasmic tail 1 [KO:K07980 ]
3821 KLRC1; killer cell lectin like receptor C1 [KO:K06541 ]
3824 KLRD1; killer cell lectin like receptor D1 [KO:K06516 ]
Compound Reference Authors Ferrara JL, Reddy P.
Title Pathophysiology of graft-versus-host disease.
Journal Reference Authors Reddy P.
Title Pathophysiology of acute graft-versus-host disease.
Journal Reference Authors Sun Y, Tawara I, Toubai T, Reddy P.
Title Pathophysiology of acute graft-versus-host disease: recent advances.
Journal Reference Authors Jaksch M, Mattsson J.
Title The pathophysiology of acute graft-versus-host disease.
Journal Reference Authors Vogelsang GB, Lee L, Bensen-Kennedy DM.
Title Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant.
Journal Reference Authors Reddy P, Ferrara JL.
Title Immunobiology of acute graft-versus-host disease.
Journal Reference Authors Blazar BR, Murphy WJ.
Title Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
Journal Reference Authors Couriel D, Caldera H, Champlin R, Komanduri K.
Title Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management.
Journal Reference Authors Jacobsohn DA, Vogelsang GB.
Title Acute graft versus host disease.
Journal Related hsa04060 Cytokine-cytokine receptor interaction
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
