In paroxysmal nocturnal hemoglobinuria (PNH), hemolysis occurs due to lack of GPI-anchored complement regulatory proteins. Which complement component, when unregulated, is the final effector of PNH hemolysis?

• A C3b acting as opsonin
• B C5b-9 (membrane attack complex) ✓
• C C1q activating classical pathway
• D C4b2a (classical pathway C3 convertase)

Explanation

In PNH, a PIGA mutation abrogates synthesis of GPI anchors, causing deficiency of CD55 (DAF, decay-accelerating factor) and CD59 (protectin) on RBC membranes. CD59 normally blocks formation of the membrane attack complex (C5b-9) by preventing insertion of C9 into the lipid bilayer. Without CD59, spontaneous alternative pathway activation proceeds to form MAC on RBC membranes, causing intravascular hemolysis. Eculizumab (anti-C5 antibody) prevents C5 cleavage and MAC formation, the therapeutic basis for PNH treatment.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.