Graft-Versus-Host-Disease

What is Graft-Versus-Host-Disease (GVHD)?

Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant, where immune cells from the donor (the graft) attack the recipient’s tissues and organs (the host). It is a potentially serious and sometimes life-threatening condition that commonly affects the skin, gastrointestinal tract, and liver, but it can also involve other organs.

GVHD occurs when the donor’s immune cells (T cells) recognize the recipient’s tissues as foreign and mount an immune response against them. There are two main types of GVHD:

• Acute GVHD: Acute GVHD typically occurs within the first 100 days after transplantation, although it can develop later. It often affects the skin, causing rash, itching, and blistering, as well as the gastrointestinal tract, leading to diarrhea, abdominal pain, nausea, and vomiting. Acute GVHD can also involve the liver, causing jaundice (yellowing of the skin and eyes) and abnormal liver function tests.

• Chronic GVHD: Chronic GVHD usually develops later, typically months to years after transplantation, although it can occur concurrently with acute GVHD. Chronic GVHD can affect multiple organs and tissues, including the skin, mouth, eyes, lungs, liver, and joints. Symptoms of chronic GVHD may include skin changes (such as thickened or hardened skin), dry mouth and eyes, shortness of breath, fatigue, muscle weakness, and joint pain.

Risk factors for GVHD include the degree of human leukocyte antigen (HLA) mismatch between the donor and recipient, the type of transplant (allogeneic vs. autologous), the source of stem cells (bone marrow, peripheral blood, or cord blood), the intensity of conditioning therapy (pre-transplant chemotherapy and/or radiation), and the use of immunosuppressive medications to prevent or treat GVHD.

What is the relationship between GVHD and oxidative stress?

The relationship between graft-versus-host disease (GVHD) and oxidative stress involves complex interactions between immune dysregulation, tissue damage, inflammation, and oxidative damage within the affected tissues and organs. Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses, leading to cellular damage and dysfunction. Several factors contribute to oxidative stress in the context of GVHD:

• Immune Dysregulation: GVHD occurs when donor-derived T cells recognize the recipient’s tissues as foreign and mount an immune response against them. This immune dysregulation leads to the release of pro-inflammatory cytokines, activation of inflammatory pathways, and recruitment of immune cells to the affected tissues. The resulting inflammatory cascade generates ROS and promotes oxidative stress within the target organs, contributing to tissue damage and dysfunction.

• Tissue Damage: GVHD primarily affects tissues with high turnover rates and active cell proliferation, such as the skin, gastrointestinal tract, and liver. The immune-mediated damage caused by GVHD disrupts the normal cellular architecture and function of these tissues, leading to epithelial cell injury, mucosal damage, and organ dysfunction. The release of ROS during inflammation and tissue injury exacerbates oxidative stress and amplifies the damage to the affected tissues.

• Inflammatory Response: The inflammatory response triggered by GVHD plays a central role in the pathogenesis of oxidative stress. Inflammatory cells such as macrophages, neutrophils, and T cells produce ROS as part of the immune response to eliminate pathogens and damaged cells. However, excessive ROS production during inflammation overwhelms the antioxidant defenses and leads to oxidative stress, further propagating tissue damage and inflammation in GVHD.

• Gastrointestinal Damage: GVHD commonly affects the gastrointestinal tract, causing mucosal damage, ulceration, and inflammation. The disruption of the intestinal barrier function allows luminal antigens and microbial products to enter the systemic circulation, triggering immune activation and systemic inflammation. The resulting inflammatory cascade generates ROS and promotes oxidative stress within the gastrointestinal mucosa, exacerbating tissue injury and dysfunction in GVHD.

• Mitochondrial Dysfunction: Oxidative stress can impair mitochondrial function and lead to mitochondrial dysfunction within the affected tissues. Mitochondrial dysfunction exacerbates ROS production and oxidative stress, further amplifying tissue damage and inflammation in GVHD.

Overall, oxidative stress plays a significant role in the pathogenesis and progression of GVHD by promoting tissue damage, inflammation, and immune dysregulation within the affected organs.