CCTC Transplant Immunology and Pharmacology 5

Question 1

A renal transplant recipient develops de novo donor-specific antibodies (DSA) against HLA-DQ7 at 18 months post-transplant, with a mean fluorescence intensity (MFI) of 4,500 on single-antigen bead assay. Which additional DSA characteristic would MOST significantly stratify this patient's risk for progressive antibody-mediated rejection (AMR) and graft loss?

Accepted Answer

C1q-binding capacity of the DSA

Answer

C1q-binding DSA indicates complement-fixing antibodies capable of activating the classical complement cascade, producing C4d deposition and endothelial injury. C1q-binding status provides functional characterization beyond MFI alone and is independently associated with inferior graft survival. Importantly, IgG4-predominant DSA are the least complement-fixing of all IgG subclasses and paradoxically may carry lower AMR risk. MFI thresholds are useful for screening but do not directly indicate complement activation potential.

Question 2

A liver transplant recipient stabilized on tacrolimus (trough 9 ng/mL) is diagnosed with invasive pulmonary aspergillosis and started on voriconazole. Seventy-two hours later, the tacrolimus trough rises to 48 ng/mL despite no dose change. The transplant coordinator anticipates this interaction. Which mechanism PRIMARILY explains this toxicity?

Accepted Answer

Voriconazole potently inhibits CYP3A4 and CYP2C19, markedly reducing tacrolimus metabolism

Answer

Tacrolimus is primarily metabolized by CYP3A4 in the liver and intestinal wall. Voriconazole is a potent inhibitor of both CYP3A4 and CYP2C19, dramatically reducing tacrolimus clearance. This interaction typically necessitates an empiric tacrolimus dose reduction of 50–75% at the time voriconazole is initiated, followed by frequent trough monitoring. Protein displacement is not clinically relevant for tacrolimus since it is extensively bound within erythrocytes, not plasma proteins.

Question 3

A kidney transplant recipient is 4 weeks post-transplant and is being considered for conversion from tacrolimus to sirolimus due to tacrolimus-induced nephrotoxicity. The surgical team raises a concern specific to early sirolimus use. Which complication is MOST directly attributable to the pharmacodynamic mechanism of mTOR inhibitors in this early post-operative setting?

Accepted Answer

Impaired wound healing and increased risk of lymphocele formation

Answer

Sirolimus inhibits mTORC1, which is essential for fibroblast proliferation, collagen synthesis, and angiogenesis — all processes required for normal wound healing. In the early post-transplant period, this creates clinically significant risks including wound dehiscence, incisional hernia, and lymphocele formation. Current guidelines recommend avoiding sirolimus conversion until at least 3 months post-transplant and ensuring complete wound healing. This is a class-specific effect of all mTOR inhibitors (sirolimus, everolimus).

Question 4

A highly sensitized kidney transplant recipient (cPRA 98%) undergoes transplantation after a negative virtual crossmatch. Immediately post-reperfusion, a protocol biopsy reveals diffuse C4d positivity in peritubular capillaries, neutrophil margination, and glomerulitis. Luminex confirms de novo DSA against HLA-A2 at MFI 11,500. Which initial treatment strategy is MOST consistent with current AMR management protocols?

Accepted Answer

Plasmapheresis with low-dose IVIG (100–200 mg/kg) after each session, combined with rituximab

Answer

Acute AMR management targets the humoral arm of the immune response. Plasmapheresis rapidly removes circulating DSA, and low-dose IVIG after each session provides immunomodulation and blunts rebound antibody synthesis. Rituximab (anti-CD20) depletes the B-cell compartment to reduce ongoing DSA production. High-dose steroids and ATG are indicated for T-cell mediated rejection, not AMR, and would be insufficient alone here. Graft nephrectomy is not indicated as an initial response to AMR when the graft is still perfused.

Question 5

A 38-year-old kidney transplant recipient is maintained on belatacept-based immunosuppression. At month 10 post-transplant, MRI reveals a solitary enhancing cerebral lesion; biopsy confirms EBV-positive monomorphic post-transplant lymphoproliferative disorder (PTLD). Which pre-transplant factor MOST directly conferred this patient's elevated risk for this specific complication?

Accepted Answer

EBV-seronegative recipient status at the time of transplant

Answer

Belatacept carries a Black Box Warning for PTLD, with the highest risk in EBV-seronegative recipients. Belatacept blocks CD28-B7 costimulation, impairing EBV-specific cytotoxic T-lymphocyte (CTL) surveillance. In EBV-seronegative recipients who lack pre-formed EBV-specific memory T cells, primary EBV infection post-transplant can drive uncontrolled B-cell proliferation in the absence of effective CTL control. Belatacept is contraindicated in EBV-seronegative transplant recipients for this reason. CMV mismatch is a risk factor for CMV disease, not EBV-related PTLD.

CCTC - Certified Clinical Transplant Coordinator Practice Test

CCTC - Certified Clinical Transplant Coordinator Practice Test

CCTC Transplant Immunology and Pharmacology 5