4 Transplantation and Immune Compatibility
Learn how transplant compatibility is assessed, how rejection and graft-versus-host disease differ, and how transplant care balances immune protection with medication risks.
Assessing transplant compatibility
Transplantation replaces diseased tissue with cells, tissue, or an organ from a donor. In an , donor antigens may trigger an immune response. Transplant care balances preserving graft function with limiting the harms of immunosuppression, especially infection and malignancy.
ABO blood-group compatibility matters because A and B antigens may be present on graft blood vessels. are highly variable cell-surface proteins that help the immune system distinguish self from non-self. HLA matching is particularly important in kidney and hematopoietic cell transplantation, although its role and relative weight vary by organ and allocation system.
A recipient may already have antibodies against donor HLA after pregnancy, blood transfusion, or a prior transplant. are antibodies that recognize the proposed donor’s HLA. HLA typing and antibody testing help estimate this risk.
A tests whether the recipient’s serum reacts with donor cells; a positive result can indicate a high risk of antibody-mediated injury. A virtual compares the recipient’s known antibody profile with the donor’s HLA type. Results are considered alongside blood group, organ-specific criteria, urgency, and other clinical factors. A match does not guarantee that rejection will not occur.
For example, if a kidney candidate has antibodies against a particular donor HLA antigen, the transplant team can assess whether the donor carries that antigen and whether a physical or virtual indicates unacceptable risk.
How graft rejection develops
Recipient T cells can recognize donor HLA directly on donor cells or recognize donor-derived peptides presented by recipient cells. B cells can produce antibodies against donor antigens. These cellular and antibody-mediated pathways can injure graft tissue and blood vessels.
develops within minutes to hours when pre-existing antibodies bind the graft and activate complement and clotting. It is now uncommon because compatibility testing screens for major risks before transplantation.
may occur at different times after transplant. T-cell-mediated rejection involves recipient T cells attacking graft tissue. Antibody-mediated rejection involves donor-specific antibodies and antibody-associated tissue injury. The mechanisms can overlap.
develops over time and involves persistent immune injury and scarring. Its effects depend on the transplanted organ.
A change in graft function does not by itself establish rejection. Infection, medication toxicity, obstruction, recurrence of the original disease, and other causes may also affect graft function. Symptoms and routine tests alone may not distinguish these causes. Evaluation is transplant- and organ-specific and may include imaging, antibody tests, or biopsy.
Graft-versus-host disease
is the reverse direction of immune attack from solid-organ rejection. In GVHD, immunocompetent donor T cells in an allogeneic hematopoietic cell transplant recognize recipient tissues as foreign and injure them; in solid-organ rejection, the recipient’s immune system attacks the donor graft.
GVHD most often affects the skin, gastrointestinal tract, and liver. Acute and chronic GVHD are clinical syndromes, and timing alone does not fully define them. Chronic GVHD can affect multiple organs and resemble autoimmune or fibrotic disease.
Prevention and treatment suppress donor immune activity. This must be balanced against infection risk and the beneficial graft-versus-tumor effect when transplantation is used to treat cancer.
Immunosuppressive treatment
Solid-organ transplantation commonly uses two phases of immunosuppression:
: Stronger treatment around the time of transplant reduces early rejection risk. Depending on the patient and transplant program, it may include an antibody-based agent and corticosteroids.
: Ongoing combination therapy. A common kidney-transplant approach combines a calcineurin inhibitor, often tacrolimus, an antimetabolite, often mycophenolate, and corticosteroids. Regimens differ by organ, rejection risk, side effects, and center protocol. Other options include mTOR inhibitors or costimulation blockers.
The medications act at different points in immune-cell activation or proliferation. Combining agents can permit effective rejection prevention, but immunosuppression also weakens defenses against infection and some cancers. Calcineurin inhibitors can cause kidney toxicity and require monitoring. Other drugs have distinct risks, including effects on blood counts, blood sugar, blood pressure, or wound healing.
Hematopoietic cell transplantation uses different conditioning and GVHD-prevention approaches. Regimens are individualized. Patients should not change or stop prescribed medicines without contacting their transplant team.
Care before and after transplantation
Before transplantation, evaluation typically considers the candidate’s overall health, existing infections, vaccination status, prior transplant-related antibodies, and ability to follow the required care plan. Infection testing helps identify active disease and guide prevention and monitoring after transplant. Vaccination needs should be reviewed in advance because some vaccines are less effective or unsuitable during substantial immunosuppression.
After transplantation, care includes monitoring graft function, drug levels when appropriate, medication effects, and signs of infection or rejection. Depending on the organ and clinical situation, the transplant team may use laboratory tests, imaging, antibody testing, or biopsy.
Taking medicines consistently and telling the team about new medicines, missed doses, or side effects are important because nonadherence or drug interactions can alter immunosuppressant exposure. Since immunosuppression increases infection risk, recipients need an individualized prevention and follow-up plan. Fever or other concerning symptoms should be reported promptly according to the team’s instructions.
A change in medication can create competing risks: reducing or interrupting a dose may raise rejection risk, while continued or increased exposure may worsen toxicity or infection risk. The transplant team should assess the individual situation and guide any adjustment.