A 4-year-old boy presents with sudden onset severe cola-colored urine, periorbital puffiness, and reduced urine output 3 weeks after a sore throat. Blood pressure is 140/95 mmHg. Urinalysis shows RBC casts, proteinuria 2+. Serum C3 is markedly reduced; C4 is normal. ASO titre is elevated. What does the selectively reduced C3 with normal C4 indicate about complement pathway activation in this disease?
- A Classical pathway activation (C4 should be low if classical pathway is involved)
- B Selective activation of the alternate complement pathway (C3 reduced, C4 normal) ✓
- C Mannose-binding lectin (MBL) pathway activation
- D Terminal complement pathway (MAC) activation without proximal pathway involvement
Correct answer: B. Selective activation of the alternate complement pathway (C3 reduced, C4 normal)
Explanation
Post-streptococcal glomerulonephritis (PSGN) characteristically activates the alternate complement pathway, explaining the pattern of reduced C3 with normal C4. In the classical pathway, both C4 and C3 are consumed. In PSGN, streptococcal neuraminidase or SPEB (a protease) directly activates the alternate pathway via properdin and Factor B, bypassing C4. This is diagnostically important: low C3 + normal C4 in a child with nephritis 2–4 weeks post-streptococcal infection = PSGN; if both C3 and C4 are low, consider SLE or membranoproliferative GN (classical pathway activation).
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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