A 23-year-old female underwent kidney transplantation. After 8 days, she suffered from acute humoral rejection. She was successfully managed with tacrolimus and one more drug that suppressed B and T lymphocytes. Drug which target both B and T lymphocytes inhibiting de novo synthesis of purines is?
**Core Concept:**
Acute humoral rejection after kidney transplantation is a severe complication caused by an excessive activation of B cells and T cells, leading to antibody production against the transplanted organ. Tacrolimus is a calcineurin inhibitor that suppresses T cell activation and calcineurin-dependent transcription, reducing the risk of rejection. Inhibition of de novo synthesis of purines is a mechanism of action for drugs that target both B and T lymphocytes.
**Why the Correct Answer is Right:**
Tacrolimus suppresses T-cell activation and calcineurin-dependent transcription, reducing antibody production and the risk of transplant rejection. It does not directly inhibit B cells or purine synthesis.
**Why Each Wrong Option is Incorrect:**
A. Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), which is involved in de novo guanine nucleotide synthesis, not purine synthesis.
B. Cyclosporine A is a calcineurin inhibitor similar to tacrolimus, but it does not target B cells directly or inhibit purine synthesis.
C. Azathioprine is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), like MMF, but it also inhibits purine synthesis. However, it does not specifically target B cells.
D. Mycophenolic acid (MPA) is the active form of MMF and inhibits IMPDH, which is involved in guanine nucleotide synthesis, not purine synthesis.
**Clinical Pearl:**
In transplant patients, an additional immunosuppressive agent is often required to target both B and T cells. MMF, an inhibitor of IMPDH, is a suitable choice for inhibiting B cell activation and purine synthesis, but not tacrolimus or cyclosporine A. Azathioprine and mycophenolic acid are suitable choices for inhibiting B cells and purine synthesis, but not MMF.
**Correct Answer:** D. Mycophenolic acid (MPA) is the active form of MMF, and inhibits inosine monophosphate dehydrogenase (IMPDH), which is involved in guanine nucleotide synthesis, not purine synthesis.