KEGG   DISEASE: H00084Help
Entry
H00084                      Disease                                

Name
Graft-versus-host disease
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.
Category
Immune system disease
BRITE hierarchy
Pathway
Graft-versus-host disease
Gene
TNF-alpha (polymorphism) [HSA:7124] [KO:K03156]
IL-10 (polymorphism) [HSA:3586] [KO:K05443]
IL1A (polymorphism) [HSA:3552] [KO:K04383]
IL-1-RA (polymorphism) [HSA:3557] [KO:K05481]
IFN-gamma (polymorphism) [HSA:3458] [KO:K04687]
IL-6 (polymorphism) [HSA:3569] [KO:K05405]
TGF-beta (polymorphism) [HSA:7040 7042 7043] [KO:K13375 K13376 K13377]
IL13 (polymorphism) [HSA:3596] [KO:K05435]
TNFRSF1B (polymorphism) [HSA:7133] [KO:K05141]
IL2 (polymorphism) [HSA:3558] [KO:K05429]
Env factor
Donor-recipient gender mismatch
Histocompatibility antigen mismatch (major and minor)
Host exposure to previous blood product transfusion
Low concentrations of immunosuppressants in recipient
Older age of both recipient and donor
Intensity of preparative regimen
Marker
TNF-alpha [HSA:7124]
TNF receptor
Drug
Cyclosporine A (CSA) [DR:D00184]
Tacrolimus (FK506) [DG:DG00439]
Methotrexate [DG:DG00681]
Corticosteroid
Mycophenolate mofetil (MMF) [DR:D00752 D05094]
Antithymocyte globulin (ATG)
Alemtuzumab [DR:D02802]
Methylprednisolone [DG:DG00410]
Daclizumab [DR:D03639]
Infliximab [DR:D02598 ]
Prednison [DG:DG00094]
Azathioprine [DG:DG00743]
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:19000150 (description, gene)
  Authors
Markey KA, MacDonald KP, Hill GR
  Title
Impact of cytokine gene polymorphisms on graft-vs-host disease.
  Journal
Tissue Antigens 72:507-16 (2008)
Reference
PMID:12394168 (gene)
  Authors
Holler E.
  Title
Cytokines, viruses, and graft-versus-host disease.
  Journal
Curr Opin Hematol 9:479-84 (2002)
Reference
PMID:18503983 (gene)
  Authors
Dickinson AM, Holler E.
  Title
Polymorphisms of cytokine and innate immunity genes and GVHD.
  Journal
Best Pract Res Clin Haematol 21:149-64 (2008)
Reference
PMID:17976248 (gene)
  Authors
Dickinson AM, Harrold JL, Cullup H.
  Title
Haematopoietic stem cell transplantation: can our genes predict clinical outcome?
  Journal
Expert Rev Mol Med 9:1-19 (2007)
Reference
PMID:15245422 (env_factor)
  Authors
Gilliam AC.
  Title
Update on graft versus host disease.
  Journal
J Invest Dermatol 123:251-7 (2004)
Reference
PMID:17784964 (env_factor, drug)
  Authors
Jacobsohn DA, Vogelsang GB.
  Title
Acute graft versus host disease.
  Journal
Orphanet J Rare Dis 2:35 (2007)
Reference
PMID:17336259 (marker)
  Authors
Ferrara JL.
  Title
Novel strategies for the treatment and diagnosis of graft-versus-host-disease.
  Journal
Best Pract Res Clin Haematol 20:91-7 (2007)
Reference
PMID:12359826 (drug)
  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)
Reference
PMID:15931364 (drug)
  Authors
Iwasaki T.
  Title
Recent advances in the treatment of graft-versus-host disease.
  Journal
Clin Med Res 2:243-52 (2004)

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