CHT Transplant Immunology 2 — Questions and Answers
Question 1: What is a 'virtual crossmatch' in transplantation?
- Predicting crossmatch outcome by comparing recipient DSA specificities to donor HLA typing without a physical test (Correct answer)
- A crossmatch performed using virtual reality imaging equipment
- A computer-simulated rejection model
- A crossmatch using stored serum from a previous transplant
Correct answer: Predicting crossmatch outcome by comparing recipient DSA specificities to donor HLA typing without a physical test
Virtual crossmatch uses recipient antibody specificity data (SAB testing) and donor HLA typing to predict whether a physical crossmatch would be positive, enabling faster organ allocation.
Question 2: Which immunosuppressive drug class specifically inhibits calcineurin to block IL-2 production and T cell activation?
- Calcineurin inhibitors (cyclosporine, tacrolimus) (Correct answer)
- mTOR inhibitors (sirolimus, everolimus)
- Antimetabolites (mycophenolate mofetil)
- Corticosteroids
Correct answer: Calcineurin inhibitors (cyclosporine, tacrolimus)
Cyclosporine and tacrolimus bind cyclophilin and FKBP12 respectively, forming complexes that inhibit calcineurin and block NFAT-mediated IL-2 gene transcription.
Question 3: In the context of sensitization, what does a high Calculated Panel Reactive Antibody (cPRA) value indicate?
- The patient has antibodies reactive to a large proportion of the donor pool, making compatible donors rare (Correct answer)
- The patient has a strong T cell response to alloantigens
- The patient is tolerant to most HLA mismatches
- The patient has low risk of rejection after transplant
Correct answer: The patient has antibodies reactive to a large proportion of the donor pool, making compatible donors rare
A high cPRA (e.g., 90%+) means the recipient has HLA antibodies that would react with most potential donors, significantly limiting compatible organ availability.
Question 4: Which test is used to measure the strength of donor-specific antibodies in mean fluorescence intensity (MFI) units?
- Single Antigen Bead (SAB) assay (Correct answer)
- Complement-dependent cytotoxicity (CDC) crossmatch
- Mixed lymphocyte reaction (MLR)
- Enzyme-linked immunosorbent assay (ELISA)
Correct answer: Single Antigen Bead (SAB) assay
SAB assays use Luminex-based beads coated with single HLA antigens to detect and quantify DSA by measuring MFI, providing antibody specificity and relative strength.
Question 5: What is the significance of 'de novo' donor-specific antibodies (dnDSA) post-transplant?
- They are strongly associated with late antibody-mediated rejection and graft loss (Correct answer)
- They are a normal immune response with no clinical consequence
- They indicate successful tolerance induction
- They only form against blood group antigens
Correct answer: They are strongly associated with late antibody-mediated rejection and graft loss
De novo DSA developing after transplantation are a major risk factor for chronic antibody-mediated rejection and long-term graft failure.
Question 6: Which phenomenon describes the situation where a transplant recipient becomes unresponsive to donor alloantigens without chronic immunosuppression?
- Operational tolerance (Correct answer)
- Clonal deletion
- Anergy induction only
- Linked suppression
Correct answer: Operational tolerance
Operational tolerance is a rare state in which a transplant recipient maintains stable graft function without immunosuppression due to active regulation of the immune response.
What is a 'virtual crossmatch' in transplantation?