A 35-year-old woman presents with hematuria, proteinuria, and hypertension after a sore throat 10 days ago. C3 is low, C4 is normal, and anti-streptolysin O (ASO) titre is elevated. Renal biopsy shows subepithelial humps ('starry sky') on electron microscopy. What is the mechanism of complement activation?

• A Classical pathway via immune complex deposition
• B Lectin pathway via mannose-binding lectin
• C Direct T-cell mediated tubular injury
• D Alternative pathway activation by streptococcal proteins ✓

Explanation

Post-streptococcal glomerulonephritis (PSGN) is mediated by the alternative complement pathway; streptococcal proteins (particularly SPEB nephritis-associated plasmin receptor, NAPlr) activate the alternative pathway, leading to selective C3 consumption with normal C4 (unlike lupus nephritis which consumes both C3 and C4 via classical pathway). Subepithelial 'humps' on EM represent immune complex deposits. The complement profile (low C3, normal C4) distinguishes alternative pathway activation. Most cases are self-limited with full recovery, particularly in children.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.