CCTC Transplant Immunology and Pharmacology 3 — Questions and Answers
Question 1: A liver transplant recipient develops biopsy-proven acute cellular rejection on day 10. AST is 450 U/L. What is the first-line treatment?
- Increase tacrolimus trough target immediately
- High-dose pulse methylprednisolone (500–1000 mg IV daily × 3 days) (Correct answer)
- Plasmapheresis and IVIG
- Antithymocyte globulin (ATG)
Correct answer: High-dose pulse methylprednisolone (500–1000 mg IV daily × 3 days)
High-dose IV methylprednisolone pulse therapy is the standard first-line treatment for acute cellular rejection in liver transplant recipients.
Question 2: Which immunosuppressant acts by inhibiting inosine monophosphate dehydrogenase (IMPDH), thereby blocking de novo purine synthesis?
- Azathioprine
- Mycophenolate mofetil (Correct answer)
- Sirolimus
- Methotrexate
Correct answer: Mycophenolate mofetil
Mycophenolate mofetil is converted to mycophenolic acid (MPA), which selectively inhibits IMPDH, blocking de novo purine synthesis that lymphocytes depend on.
Question 3: In the context of transplantation, what does a positive crossmatch using complement-dependent cytotoxicity (CDC) indicate?
- The donor has high panel reactive antibody (PRA)
- The recipient has preformed antibodies that lyse donor lymphocytes (Correct answer)
- The recipient lacks HLA antibodies to the donor
- There is ABO incompatibility between donor and recipient
Correct answer: The recipient has preformed antibodies that lyse donor lymphocytes
A positive CDC crossmatch indicates recipient serum contains preformed antibodies that bind donor lymphocytes and, with complement, cause their lysis—a contraindication to transplant.
Question 4: Which of the following best describes the mechanism of antithymocyte globulin (ATG) in transplant immunosuppression?
- Binds CD25 on activated T cells to block IL-2 signaling
- Polyclonal antibodies that deplete T lymphocytes via complement and ADCC (Correct answer)
- Inhibits calcineurin to prevent IL-2 gene transcription
- Blocks CD80/86 on antigen-presenting cells
Correct answer: Polyclonal antibodies that deplete T lymphocytes via complement and ADCC
ATG is a polyclonal antibody preparation that depletes T lymphocytes through complement-mediated lysis and antibody-dependent cellular cytotoxicity (ADCC).
Question 5: A transplant coordinator is reviewing immunosuppression for a patient with EBV-negative serostatus receiving a kidney from an EBV-positive donor. What post-transplant complication requires heightened monitoring?
- Cytomegalovirus (CMV) end-organ disease
- Post-transplant lymphoproliferative disorder (PTLD) (Correct answer)
- BK virus nephropathy
- Cryptococcal meningitis
Correct answer: Post-transplant lymphoproliferative disorder (PTLD)
EBV-seronegative recipients receiving organs from EBV-positive donors are at high risk for PTLD because primary EBV infection occurs in the setting of intense immunosuppression.
Question 6: Which mechanism explains why corticosteroids are effective as both induction and maintenance immunosuppression in transplantation?
- They selectively deplete CD8+ cytotoxic T cells
- They block NF-κB, reducing transcription of pro-inflammatory cytokines including IL-1, IL-6, and TNF-α (Correct answer)
- They inhibit mTOR-mediated T-cell proliferation
- They increase regulatory T-cell counts by upregulating FoxP3 expression
Correct answer: They block NF-κB, reducing transcription of pro-inflammatory cytokines including IL-1, IL-6, and TNF-α
Corticosteroids bind glucocorticoid receptors and block NF-κB activation, broadly reducing transcription of multiple pro-inflammatory cytokines essential for alloimmune responses.
Question 7: When monitoring a heart transplant patient's tacrolimus levels, which specimen type and timing is standard practice?
- Peak level 2 hours after morning dose
- Random level at any time of day
- Trough level (C0) drawn just before the morning dose (Correct answer)
- 4-hour post-dose AUC measurement
Correct answer: Trough level (C0) drawn just before the morning dose
Tacrolimus trough levels (C0), drawn immediately before the next scheduled dose, are the standard pharmacokinetic monitoring parameter used to guide dosing.
CCTC Transplant Immunology and Pharmacology 3
A liver transplant recipient develops biopsy-proven acute cellular rejection on day 10.
AST is 450 U/L.
What is the first-line treatment?