Graft-versus-host disease

Definition:

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.

References:

[1]. A M Dickinson, et al. Polymorphisms of cytokine and innate immunity genes and GVHD. Best Pract Res Clin Haematol. 2008 Jun;21(2):149-64. [Content Brief]

[2]. Anita C Gilliam, et al. Update on graft versus host disease. J Invest Dermatol. 2004 Aug;123(2):251-7. [Content Brief]

[3]. Anne M Dickinson, et al. Haematopoietic stem cell transplantation: can our genes predict clinical outcome?. Expert Rev Mol Med. 2007 Nov 2;9(29):1-19. [Content Brief]

[4]. Ernst Holler, et al. Cytokines, viruses, and graft-versus-host disease. Curr Opin Hematol. 2002 Nov;9(6):479-84. [Content Brief]

[5]. K A Markey, et al. Impact of cytokine gene polymorphisms on graft-vs-host disease. Tissue Antigens. 2008 Dec;72(6):507-16. [Content Brief]

[6]. Ming-Tseh Lin, et al. Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med. 2003 Dec 4;349(23):2201-10. [Content Brief]

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