Organ Transplantation and Graft Classification

• Transplantation is the process of transferring an organ or part of an organ (graft) from a donor to themselves or another recipient.
• Histocompatibility between donor and recipient minimizes transplant rejection risk.
• Immunosuppressive therapy, close follow-up, and infection prevention are required.

Classification of Grafts by Donor-Recipient Relationship

• Autografts: Grafts are transferred from one part of an individual to another location on the same individual.
• Skin grafts, the saphenous vein, and hair transplants are examples of autografts.
• Isografts (syngeneic grafts): Grafts are transferred between genetically identical individuals, specifically identical twins.
• Allografts: Grafts are transferred between non-genetically identical individuals of the same species.
• Xenografts: Grafts are transferred between different species. An example is between humans and animals.

Classification of Grafts by Anatomic Location

• Orthotopic graft: Grafts or organs are placed in their normal anatomical location.
• The liver, lung, and heart are examples of orthotopic locations for grafts.
• Heterotopic graft: Tissue grafts or organs are placed into a site other than their normal location.
• The kidney and pancreas are examples of heterotopic locations for grafts.

Sources of Hematopoietic Stem Cell Grafts

• Umbilical cord blood
• Bone marrow
• Peripheral blood stem cell

Major Histocompatibility Complexes (MHC) and Human Leukocytes Antigens (HLA)

• HLA: Genes on chromosome 6 code for MHC molecules.
• MHC: These are proteins present on the surface of cells.

Types of MHC

• Class I MHC: Code for HLA-A, HLA-B, and HLA-C.
• Class II MHC: Code for HLA-DR, HLA-DP, and HLA-DQ.
• MHC has a high degree of polymorphism.
• The inheritance type for MHC is codominance.
• The strongest immunogens lead to grafts rejection.

Tests for Organ Matching

• ABO Compatibility: ABO compatibility is required for solid organ transplantation.
• Histocompatibility (HLA Typing): Histocompatibility (HLA) typing is required for stem cell and solid organ transplantation.
• HLA-A, HLA-B, and HLA-DR types are tested via PCR (Polymerase Chain Reaction) test.
• Crossmatching (Lymphocytotoxicity) Test: Recipient serum is examined for antibodies against the donor's T and B lymphocytes.

Types of Tissue Rejection

• Hyperacute
• Acute
• Chronic
• Graft versus host Rejection

Hyperacute Rejection

• Onset: Occurs < 48 hours after transplantation, usually within minutes to hours.
• Frequency: <1%
• Risk factors: ABO incompatibility, and HLA incompatibility.
• Pathophysiology:
  • Preformed antibodies against MHC class I antigens result from exposure to foreign AB or HLA class I during pregnancy, transfusion, or a previously rejected transplant.
  • Humoral rejection (type II hypersensitivity reaction): Preformed antibodies bind donor's cells, activating the complement, NK cells, and phagocytes, leading to graft ischemia and necrosis.
• Graft removal is the treatment.
• Prevention involves preoperative crossmatching and ABO grouping.

Acute Rejection

• Frequency: Accounts for approximately 50% of post-transplant organ dysfunction.
• Onset: Occurs > 48 hours - 6 months after transplantation (usually within weeks to months).
• Risk factors: HLA incompatibility, and inadequate immunosuppression.
• Pathophysiology:
  • Type IV hypersensitivity reaction: CD4+ T cells activate into Th1 cells leading to INF-γ and IL-2 production which activates macrophage and CD8 T cells recruitment, causing CD8+ cells to react with the donor MHC class I antigens, damaging cells directly.
  • Type II hypersensitivity reaction: antibodies react against the donor HLA antigens, activating the complement, NK cells, and phagocytes.
• Treatment: Adjust dosage of immunosuppressive therapy.
  • Type IV reaction:
    • High-dose glucocorticoids
    • Administer Anti-T-cell antibody
  • Type II reaction:
    • Plasmapheresis
    • Administer Anti-CD20 antibodies
    • Administer Anti-T-cell antibody
    • Corticosteroids are used for treatment.
• Prevention involves preoperative HLA matching & crossmatching and post-transplant immunosuppressive therapy.

Chronic Rejection

• Frequency: Accounts for ~ 50% of post-transplant organ dysfunction.
• Onset: Occurs > 6 months (usually after a few years)
• Risk Factors: Previous acute rejection, prolonged cold ischemia time, and inadequate immunosuppression
• Pathophysiology:
  • Cellular rejection (type IV hypersensitivity reaction)
  • Humoral rejection (type II hypersensitivity reaction)
• Graft removal is the treatment.
• No known prevention exists.

Graft Versus Host Rejection

• This is where the donor's immune cells recognize the recipient cells as foreign. As a result, the rejection initiates an immune reaction and systemic inflammation.
• Affected organs: Skin, gastrointestinal tract, liver, lungs, eyes, mouth, joints.
• Risk factor: The transplantation of lymphocyte-rich organs.
  • Hematopoietic stem cell
  • Small bowel transplantation.

Organ transplantation involves transferring organs or tissues from a donor to a recipient. Grafts can be classified by donor-recipient relationship (autografts, isografts, allografts, xenografts) or anatomic location (orthotopic). Histocompatibility is crucial to minimize rejection.