A 7-year-old boy has recurrent severe pyogenic infections caused by encapsulated bacteria. Complement studies show a profoundly reduced C3 level with normal C4, and impaired opsonization. Genetic analysis reveals a mutation inactivating a serine protease that normally cleaves C3b and C4b. The defective protein is:

• A Factor H
• B Properdin
• C Factor D
• D Factor I ✓

Explanation

Factor I is the serine protease that degrades active C3b and C4b into inactive fragments. Its absence allows unchecked formation and cycling of the alternative pathway C3 convertase, consuming C3 systemically. The result is very low C3 with normal C4 (since C4 is not consumed by the alternative pathway loop) and recurrent infections with pyogenic organisms, especially Neisseria and encapsulated bacteria. Factor H accelerates decay of the convertase but does not proteolytically cleave C3b itself.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.