International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 167-176 http://medscipublisher.com/index.php/ijmms 168 1 The Pathogenesis and Influencing Factors of GVHD 1.1 The pathogenesis of GVHD Graft-versus-host disease (GVHD) is a complex immune mediated response that may occur after allogeneic hematopoietic stem cell or organ transplantation. Its pathogenesis mainly involves three stages: activation of the host immune system, activation and proliferation of immune cells, and ultimately attack on the host tissue. During the transplantation process, the donor's T cells are activated and rapidly proliferate upon contact with the host's allogeneic human leukocyte antigen (HLA). These T cells release a large amount of cytokines, such as interferon γ And tumor necrosis factor α. These factors not only enhance the activity of T cells, but also attract other immune cells such as macrophages to participate in the response. Activated immune cells then attack the host's skin, liver, and gastrointestinal tissues, leading to clinical manifestations of GVHD. Ferrara and Chaudhry (2018) described how acute GVHD targets the crypts responsible for intestinal mucosal self-renewal in the intestine (Figure 1). The latest advances in the recognition and cultivation of intestinal stem cells have improved scientists' understanding of the interactions between the microbiota and the immune system (including innate and adaptive), which are key to the pathophysiology of GVHD. Serum biomarkers obtained from the gut are the most predictive of long-term outcomes of GVHD, and these biomarkers focus on cellular elements that serve as protective barriers and targets for GVHD. Figure 1 Early acute GI GVHD (Ferrara and Chaudhry, 2018) Toubai et al. (2008) discussed and compared the pathophysiology of acute and chronic GVHD. Acute GVHD typically manifests within 100 days after HSCT (hematopoietic stem cell transplantation), triggered by a response of donor T cells to host polymorphic histocompatibility antigens. Chronic GVHD usually manifests after 100 days and has certain characteristics of autoimmune diseases. It may be newly developed, or it may be a continuation of acute GVHD after resolution. The pathogenesis of GVHD includes the T cell-mediated characteristics of the disease, interactions with the microbiota, and differences between acute and chronic forms. Through these studies, a more comprehensive perspective on the complexity and management strategies of the disease can be obtained. 1.2 Factors affecting the occurrence of GVHD The occurrence and severity of GVHD are influenced by various factors. Among them, HLA typing differences between donors and recipients are an important factor; Transplantation with HLA matching typically has a lower risk of GVHD. In addition, the gender, age, and genetic background of the donor and recipient can also affect the risk of GVHD. For example, transplantation from young female donors to older male recipients may increase the incidence of GVHD. The pre-transplantation treatment plan, including the intensity of chemotherapy and/or
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