During acute inflammation, the NET (neutrophil extracellular trap) formation involves release of chromatin and granule proteins to trap and kill microorganisms. However, excessive NETosis is implicated in the pathogenesis of which of the following conditions?
- A SLE — anti-dsDNA antibodies recognizing NET-derived DNA ✓
- B Chronic granulomatous disease (CGD) — failure to kill catalase-positive organisms
- C Chediak-Higashi syndrome — defective granule trafficking
- D Leukocyte adhesion deficiency — absent CD18 expression
Explanation
NETs (neutrophil extracellular traps) consist of decondensed chromatin studded with antimicrobial proteins (histones, elastase, MPO). Excessive or impaired NET clearance releases nuclear material (including dsDNA and histones) that can trigger autoantibody formation. In SLE, impaired DNase I activity (encoded by DNASE1L3 mutations in some familial cases) leads to accumulation of NETs; auto-antibodies including anti-dsDNA, anti-histone, and anti-NET antibodies are generated. NETs contribute to endothelial damage, thrombosis (NETosis in COVID-19/APS), and renal injury in 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.