A 45-year-old woman presents with subacute progressive limb weakness, bilateral leg paraesthesias, and is found to have oligoclonal bands in CSF but not serum. MRI brain shows periventricular T2 lesions perpendicular to the corpus callosum (Dawson fingers). Visual evoked potentials are delayed. What is the mechanism of first-line disease-modifying therapy (DMT) with interferon beta-1a in this condition?
- A Selective sphingosine-1-phosphate receptor modulation sequestering lymphocytes in lymph nodes
- B Inhibition of T-lymphocyte migration across the blood-brain barrier via downregulation of matrix metalloproteinases ✓
- C CD20-mediated B-cell depletion
- D Inhibition of dihydroorotate dehydrogenase reducing lymphocyte proliferation
Correct answer: B. Inhibition of T-lymphocyte migration across the blood-brain barrier via downregulation of matrix metalloproteinases
Explanation
This patient has relapsing-remitting multiple sclerosis (RRMS). Interferon beta-1a (Avonex, Rebif) exerts its immunomodulatory effect by downregulating matrix metalloproteinases and adhesion molecules, thereby reducing T-lymphocyte and monocyte transmigration across the blood-brain barrier. It also shifts cytokine balance from Th1 (proinflammatory) to Th2. Sphingosine-1-phosphate receptor modulation is the mechanism of fingolimod. CD20 B-cell depletion is the mechanism of ocrelizumab/ofatumumab. Dihydroorotate dehydrogenase inhibition is teriflunomide's mechanism.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.