A 24-year-old woman presents with haematuria, proteinuria, and hypertension 10 days after a throat infection. Kidney biopsy shows diffuse endocapillary hypercellularity and 'humps' on electron microscopy. Immunofluorescence shows 'starry sky' C3 predominant granular deposits. Serum C3 is low and C4 is normal. Which pathway of complement is primarily activated in this condition?
- A Classical pathway, activated by IgG antibodies against streptococcal M-protein
- B Alternative pathway, activated by the planted streptococcal antigen SPEB/SpeB (streptococcal pyrogenic exotoxin B) directly activating C3 ✓
- C Lectin pathway, activated by mannose-binding lectin binding streptococcal carbohydrates
- D Terminal pathway, directly activated by nephrin-SPEB immune complexes
Correct answer: B. Alternative pathway, activated by the planted streptococcal antigen SPEB/SpeB (streptococcal pyrogenic exotoxin B) directly activating C3
Explanation
Post-streptococcal glomerulonephritis (PSGN) classically causes low C3 with normal C4, a pattern indicating predominant alternative pathway activation (which consumes C3 without using C4). The streptococcal antigen SpeB (cysteine protease/pyrogenic exotoxin B) and GAPDH are planted in the glomerulus and directly activate the alternative C3 convertase. The 'starry sky' C3-dominant IF pattern with subepithelial humps on EM confirms this. Classical pathway activation (low C3 AND C4) would be seen in membranoproliferative GN or lupus nephritis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.