Which of the following immunosuppressants is a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH) and is preferentially used in lupus nephritis and post-transplant lymphoproliferative disorder (PTLD)?

Explanation

## Mycophenolate Mofetil (MMF): IMPDH Inhibition **Key Point:** Mycophenolate mofetil (MMF) is a selective, non-competitive inhibitor of IMPDH type II, the rate-limiting enzyme in guanosine nucleotide synthesis in T and B lymphocytes. ### Mechanism of Action 1. MMF is a prodrug; rapidly hydrolyzed to mycophenolic acid (MPA) 2. MPA inhibits IMPDH type II (preferentially expressed in lymphocytes) 3. Blocks guanosine monophosphate (GMP) synthesis 4. Depletes guanosine nucleotides in T and B cells 5. Suppresses proliferation of T and B lymphocytes without affecting other cell types **High-Yield:** MMF is lymphocyte-selective because IMPDH type II is the predominant isoform in T and B cells; other cell types use the salvage pathway and are less affected. ### Clinical Advantages and Indications | Indication | Rationale | |-----------|----------| | Lupus nephritis | Reduces proteinuria and slows renal disease progression | | Post-transplant lymphoproliferative disorder (PTLD) | Prevents EBV-driven B-cell proliferation | | Organ transplant (renal, cardiac, hepatic) | Part of standard triple-therapy regimen | | Autoimmune diseases | Steroid-sparing effect in SLE, vasculitis | **Clinical Pearl:** MMF is often combined with calcineurin inhibitors (tacrolimus/cyclosporine) and corticosteroids in transplant protocols because it acts at a different point in the immune cascade, reducing rejection rates without overlapping toxicity. **Warning:** GI side effects (diarrhea, nausea, abdominal pain) are common and dose-limiting; enteric-coated mycophenolate sodium (EC-MPS) is an alternative formulation. **Mnemonic:** **MMF = Guanosine Blocker** — Remember IMPDH blocks the synthesis of guanosine nucleotides, which are essential for lymphocyte proliferation.