A patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) has a PIGA somatic mutation. This leads to hemolysis because:
- A Complement activation via classical pathway is triggered by IgG autoantibodies to PIGA
- B PIGA mutation activates intrinsic apoptosis via cytochrome c release
- C Loss of GPI-anchored CD55 and CD59 renders erythrocytes susceptible to complement-mediated lysis ✓
- D Loss of GPI anchor prevents hemoglobin oxygen loading, causing oxidative hemolysis
Correct answer: C. Loss of GPI-anchored CD55 and CD59 renders erythrocytes susceptible to complement-mediated lysis
Explanation
PIGA encodes a phosphatidylinositol glycan class A protein essential for GPI anchor biosynthesis. Without GPI anchor, erythrocytes lack CD55 (decay-accelerating factor) and CD59 (membrane inhibitor of reactive lysis), both complement regulatory proteins. Unregulated alternative pathway complement activation on erythrocyte surfaces results in MAC-mediated hemolysis. The condition is not IgG-mediated and does not involve intrinsic apoptosis or impaired oxygen binding.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.