| H00084 | |
| H number | H00084 |
| 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 DIS_PATHWAY hsa05332 Graft-versus-host disease |
| Network | - |
| Gene | IL10 [HSA:3586] [KO:K05443] TNF [HSA:7124] [KO:K03156] IL1A [HSA:3552] [KO:K04383] IL1RN [HSA:3557] [KO:K05481] IFNG [HSA:3458] [KO:K04687] IL6 [HSA:3569] [KO:K05405] TGFB1 [HSA:7040] [KO:K13375] TGFB2 [HSA:7042] [KO:K13376] TGFB3 [HSA:7043] [KO:K13377] IL13 [HSA:3596] [KO:K05435] TNFRSF1B [HSA:7133] [KO:K05141] IL2 [HSA:3558] [KO:K05429] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Ruxolitinib phosphate [DR:D09960] Ibrutinib [DR:D10223] Abatacept [DR:D03203] Belumosudil mesylate [DR:D11816] |
| Comment | - |
| Other DBs | ICD-11: 4B24 ICD-10: T86 MeSH: D006086 OMIM: 614395 |
| Reference | PMID:19000150 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) DOI:10.1111/j.1399-0039.2008.01139.x PMID:12394168 AUTHORS Holler E. TITLE Cytokines, viruses, and graft-versus-host disease. JOURNAL Curr Opin Hematol 9:479-84 (2002) DOI:10.1097/00062752-200211000-00002 PMID:18503983 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) DOI:10.1016/j.beha.2008.03.004 PMID:17976248 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) DOI:10.1017/S1462399407000488 PMID:15245422 AUTHORS Gilliam AC. TITLE Update on graft versus host disease. JOURNAL J Invest Dermatol 123:251-7 (2004) DOI:10.1111/j.1523-1747.2004.23211.x PMID:14657427 (IL10) AUTHORS Lin MT, Storer B, Martin PJ, Tseng LH, Gooley T, Chen PJ, Hansen JA TITLE Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. JOURNAL N Engl J Med 349:2201-10 (2003) DOI:10.1056/NEJMoa022060 |