Paroxysmal nocturnal haemoglobinuria (PNH) results from a somatic PIG-A mutation in a haemopoietic stem cell, leading to deficiency of GPI-anchored proteins. Which two proteins are most critical for complement regulation, and their absence leads to intravascular haemolysis?

• A CD4 and CD8
• B Factor H and Factor I
• C C3 and C5
• D CD55 (DAF) and CD59 (protectin) ✓

Explanation

PNH cells lack GPI-anchored complement regulatory proteins: CD55 (decay-accelerating factor, DAF) which accelerates decay of C3/C5 convertases, and CD59 (protectin/MIRL) which blocks MAC (C5b-9) assembly on the cell membrane. Without these, complement attack (particularly through the alternative pathway, amplified at low blood pH during sleep) lyses PNH cells, causing intravascular haemolysis, haemoglobinuria, and thrombosis. Eculizumab/ravulizumab (anti-C5 monoclonal antibodies) block MAC formation and are the treatment of choice.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.