105 Host Versus Graft Disease (HvGD) and Graft Versus Host Disease (GvHD)

Host Versus Graft Disease (HvGD):

HvGD occurs when the host’s immune system destroys the transplanted graft. This immune response is primarily driven by the host’s T cells or antibodies attacking the non-self MHC I molecules present on the graft tissue.

Mechanism of HvGD:
The host’s immune system perceives the graft’s MHC molecules as foreign, leading to an immune response against the transplanted tissue.

Prevention Strategies for HvGD:
To prevent HvGD, it is crucial to ensure that the blood types of the recipient and donor match and to perform cross-reaction lab tests before the transplantation. This helps confirm that the recipient’s blood does not contain antibodies or white blood cells that would react adversely with the donor’s blood. Additionally, matching the donor and recipient’s Major Histocompatibility Complex (MHC), also known as human leukocyte antigens (HLA), is essential to minimize the risk of rejection.

Treatment Options for HvGD:  Immunosuppressants
Administering immunosuppressive drugs immediately after transplantation is a standard treatment to prevent rejection. Commonly used drugs include prednisone, a glucocorticoid, and cyclosporine, which suppresses T cell activity. Other drugs used include those that suppress both B and T cell proliferation and activity.

Long-term Considerations:
While immunosuppressive therapy is effective in preventing graft rejection, it comes with long-term risks, including an increased likelihood of infections and cancer (such as lymphoma, skin cancer, cervical cancer, and colon cancer). Additionally, there is a potential for kidney damage and periodontal disease in patients undergoing long-term immunosuppressive treatment.

Graft Versus Host Disease (GvHD):

GvHD is a condition where the immune cells, primarily T cells, from a transplanted organ or tissue attack the recipient’s body. There are two main types of GvHD:

1. Allogeneic GvHD: This occurs when an immunocompromised individual receives a graft of lymphoid tissue that contains active white blood cells, such as grafts/transplants of bone marrow, spleen, intestines, or stem cells from another person.
2. Autologous GvHD: This occurs when an individual receives their own hematopoietic stem cells. It is generally milder than allogeneic GvHD and often resolves without treatment, but in rare cases, it can present symptoms similar to allogeneic GvHD and be life-threatening.

Two Time Frames:
GvHD symptoms can manifest in two phases:

• Acute: Symptoms appear within days to weeks post-transplant and can either resolve or become chronic. Acute symptoms include itchy pruritis dermatitis, hepatitis, and enteritis, causing itch skin rashes, loss of appetite, weight loss, jaundice, diarrhea, intestinal cramping and pain.
• Chronic: Symptoms start more than three months after the transplant and can last a lifetime, presenting as dry eyes, photophobia, dry mouth, fatigue, arthralgia, skin rashes, muscle weakness, myalgia, weight loss, premature graying, pericarditis, and shortness of breath (due to lung damage).

Common Scenario of Allogeneic GvHD:
Allogeneic GvHD is frequently associated with bone marrow transplants where the donor’s T cells attack the recipient’s cells. This process typically begins with the eradication of the recipient’s bone marrow, followed by the transplantation of donor bone marrow containing active white blood cells. The donor’s immune cells then recognize the recipient’s cells as foreign and launch an immune attack.  It should be noted that an identical MHC match in an allogeneic donation is a preventative measure, but is usually only possible when close blood relatives are involved as donors.  GvHD most commonly occurs as a result of allogeneic bone marrow transplants in which the MHC alleles are not an exact match.  In this case, it is usually the non-matching MHC molecules on the recipient’s cells that are attacked by the donor’s T cells.  That being said, allogeneic GvHD can even occur when there is an identical MHC match between donor and recipient.  In this case of allogenic GvHD, instead of the MHC molecules, it is the minor histocompatibility (minor H) antigens that are targeted by the donor’s T cells.  B cells may be involved in these scenarios as well as research has found that suppressing B cell activity can help alleviate some symptoms.

Other Scenarios Leading to GvHD:
GvHD can also occur in immunocompromised individuals, such as neonates or patients undergoing chemotherapy or radiation therapy, who receive transfusions of unirradiated blood products.

Side Note:  Gamma irradiation of blood products is performed to reduce the number of lymphocytes present and offset the chance of GvHD occurring.

Example of Autologous GvHD:
This is most commonly seen in individuals with multiple myeloma, a cancer that affects bone marrow. During treatment, high-dose chemotherapy can destroy healthy bone marrow cells. Prior to treatment, hematopoietic stem cells are collected from the patient and transplanted back post-chemotherapy. Rarely, these transplanted hemapoietic stem cells lead to an autoimmune attack of the body, potentially due to triggering an excessive increase in antigen presentation levels and/or inducing T cell hyperreactivity.

GvHD Treatment Options:
Prevention involves ensuring a close MHC match between donor and recipient. Post-transplant, immunosuppressants are administered to prevent GvHD. Common drugs include prednisone, cyclosporine, and other medications that suppress both B and T cell proliferation. Long-term use of immunosuppressants can increase the risk of infections, cancer, kidney damage, and periodontal disease, including gingival hyperplasia.  Gingival hyperplasia is often a symptom of poor oral hygiene, and is characterized by an overgrowth of gum tissue (gingivae) that is susceptible to bleeding and pain.  Maintaining good hygiene is emphasized to reduce infection risk.

Summary

• Host Versus Graft Disease (HvGD):
  • Definition: The host’s immune system destroys the graft (transplant).
  • Mechanism: Host’s T cells or antibodies attack the transplanted tissue, most often directed at the non-self MHC I molecules on the graft tissue.
  • Treatment Options:
    • Prevention:  Blood types of recipient and donor must match and cross-reaction lab test must be performed prior to donation to ensure the recipient’s blood doesn’t contain antibodies or WBCs that react (i.e., are not compatible) with the donor’s blood.  Ensure a close MHC (HLA) match between donor and recipient.
    • Immunosuppressants: Administered immediately after transplantation to prevent rejection.
      • • Common Drugs:
        • Prednisone (glucocorticoid)
        • Cyclosporine (suppresses T cell activity)
        • Other drugs suppress both B and T cells.
      • Long-term Considerations:
      • Increased risk of infection.
      • Increased risk of cancer (lymphoma, skin cancer, cervical cancer, colon cancer).
      • Potential for kidney damage and periodontal disease.

• Graft Versus Host Disease (GvHD):
  • Definition: The donated organ or tissue attacks the host’s body.
  • Scenario: Common in bone marrow transplants.
    • Process:
      • Recipient’s bone marrow is eradicated (often due to cancer).
      • Transplanted bone marrow contains donor’s white blood cells.
      • Donor’s white blood cells (e.g., T cells) recognize recipient’s cells as foreign and attack.
    • Affected Tissues: Skin, liver, and gastrointestinal tract.
  • Treatment Options:
    • Prevention: Close MHC (HLA) match.
    • Immunosuppressants: Given post-transplant to prevent GvHD.
      • Common Drugs:
        • Prednisone (glucocorticoid)
        • Cyclosporine (suppresses T cell activity)
        • Other drugs that suppress both B and T cells.
    • Long-term Considerations:
      • Increased risk of infection.
      • Increased risk of cancer.
      • Potential for kidney damage and periodontal disease.
      • Emphasis on maintaining good hygiene to reduce infection risk.