Transplant

Snapshot

A 60-year-old-man presents with nausea and vomiting to his primary care physician. Medical history is significant for a liver transplantation approximately 2 weeks prior to presentation. On physical examination there is scleral icterus and mild ascites. A liver biopsy shows lymphocytic infiltrates in the interstitium. (Acute rejection)

Introduction

Transplantation is a process by which
- cells, tissues, or organs (a graft) from the donor are transplanted into a host (or recipient)
The immune system’s ability to recognize and respond to foreign antigens bring challenges to transplantation
There are several types of grafts
- autograft
  - tissue is moved from one location to another in the same person
    - e.g., skin graft and using the saphenous vein to replace a coronary artery
  - the graft will not be considered foreign and thus
    - will not require lifelong immunosuppresion
- syngeneic graft (isograft)
  - tissue is transplanted from one genetically identical donor to the host
    - e.g., transplantation between monozygotic twins
- allograft
  - tissue is transplanted from one genetically different donor of the same species to the host
    - e.g., kidney transplant
- xenograft
  - tissue is transplanted from a donor of a different species to the host
e.g., porcine heart valve

Transplant Rejection

Transplant Rejection
Rejection Type	Pathogenesis	Comments
Hyperacute	Type II hypersensitivity reaction where pre-existing recipient antibodies attack the donor antigen resulting incomplement activationendothelial damageinflammationthrombosis	Timeminutes to hoursFindingscapillary thrombosis whichprevents graft vascularization
Acute	Cellular rejectiontype IV hypersensitivity reaction whererecipient CD8+ T-cells react to donor antigens after activation by antigen presenting cells Humoral rejectionjust like in hyperacute rejection; however,the antibodies are formed after transplantation occured	Timeweeks to monthsFindings graft vessel vasculitis withlymphocytic infiltrates
Chronic	Type II and IV hypersensitivity reaction secondary toCD4+ T-cells responding to the host’s antigen presenting cells	Timemonths to yearsFindingscytokine secretion after T-cell activation leads tosmooth muscle proliferationinterstitial fibrosisparenchymal atrophy
Graft-versus-host disease	Type IV hypersensitivity reaction secondary to the donor’s T-cells attacking the recipient’s cells leading to organ dysfunction	TimevariableFindingsmaculopapular rashjaundicediarrheahepatosplenomegaly

Tissue Compatibility Testing

ABO blood typing
Tissue typing
- used to see if HLA antigens match and focuses on
  - HLA-A
  - HLA-B
  - HLA-DR