CCTC Transplant Immunology and Pharmacology 4 — Questions and Answers
Question 1: A renal transplant recipient is found to have donor-specific antibodies (DSAs) against HLA-DQ7 at 18 months post-transplant with a stable creatinine. This finding is best described as:
- Subclinical antibody-mediated rejection requiring immediate plasma exchange
- De novo DSA, a risk factor for chronic allograft nephropathy warranting close surveillance (Correct answer)
- A benign finding that requires no intervention
- Evidence of ABO incompatibility developing late post-transplant
Correct answer: De novo DSA, a risk factor for chronic allograft nephropathy warranting close surveillance
De novo DSA development post-transplant is strongly associated with chronic antibody-mediated rejection and allograft loss, warranting biopsy consideration and protocol intensification.
Question 2: Which drug interaction poses the greatest risk of calcineurin inhibitor toxicity in a transplant recipient?
- Metoprolol added for hypertension
- Azithromycin added for community-acquired pneumonia
- Fluconazole added for oral candidiasis (Correct answer)
- Trimethoprim-sulfamethoxazole added for PCP prophylaxis
Correct answer: Fluconazole added for oral candidiasis
Fluconazole is a potent CYP3A4 inhibitor that dramatically increases tacrolimus and cyclosporine levels, often causing 2–5 fold elevations within days of initiation.
Question 3: What is the role of regulatory T cells (Tregs) in transplant tolerance?
- They directly kill donor cells presenting alloantigens
- They suppress effector T-cell responses to donor antigens, promoting graft acceptance (Correct answer)
- They produce IL-17 to recruit neutrophils to the graft
- They activate B cells to produce donor-specific antibodies
Correct answer: They suppress effector T-cell responses to donor antigens, promoting graft acceptance
FoxP3+ regulatory T cells suppress alloreactive effector responses through IL-10, TGF-β, and direct cell contact, playing a central role in operational tolerance.
Question 4: A kidney transplant recipient develops BK virus nephropathy confirmed on biopsy. What is the recommended management approach?
- Add cidofovir to current immunosuppression regimen
- Reduce overall immunosuppression, particularly the antimetabolite (Correct answer)
- Initiate high-dose ganciclovir therapy
- Begin pulse steroids to treat concurrent cellular rejection
Correct answer: Reduce overall immunosuppression, particularly the antimetabolite
The primary treatment for BK nephropathy is reduction of immunosuppression—typically by halving or stopping the antimetabolite—to restore antiviral immunity.
Question 5: Which allorecognition pathway involves recipient T cells recognizing intact donor MHC molecules presented directly on donor antigen-presenting cells?
- Indirect allorecognition
- Direct allorecognition (Correct answer)
- Semi-direct allorecognition
- Linked allorecognition
Correct answer: Direct allorecognition
Direct allorecognition occurs when recipient T cells recognize intact donor HLA molecules on donor-derived APCs, driving early acute rejection with high precursor frequency.
Question 6: A patient is receiving induction therapy with basiliximab. What is the mechanism of this agent?
- Polyclonal T-cell depletion via complement-mediated lysis
- Chimeric monoclonal antibody that blocks the IL-2 receptor alpha chain (CD25) on activated T cells (Correct answer)
- Inhibition of calcineurin to prevent NFAT nuclear translocation
- Costimulation blockade via CTLA4-Ig fusion protein
Correct answer: Chimeric monoclonal antibody that blocks the IL-2 receptor alpha chain (CD25) on activated T cells
Basiliximab is a chimeric anti-CD25 monoclonal antibody that blocks IL-2Rα on activated T cells, preventing IL-2–driven clonal expansion without T-cell depletion.
Question 7: In pharmacokinetic monitoring of mycophenolate mofetil, what parameter most accurately predicts clinical outcomes compared to trough levels alone?
- Peak concentration (Cmax) at 2 hours post-dose
- Area under the concentration-time curve (AUC0–12) (Correct answer)
- Random mid-dose MPA concentration
- Pre-dose trough level measured at 12 hours
Correct answer: Area under the concentration-time curve (AUC0–12)
MPA AUC0–12 is the most reliable predictor of both rejection and toxicity; abbreviated AUC using 3-point sampling strategies are used clinically as surrogates.
CCTC Transplant Immunology and Pharmacology 4
A renal transplant recipient is found to have donor-specific antibodies (DSAs) against HLA-DQ7 at 18 months post-transplant with a stable creatinine.
This finding is best described as: