In SLE pathogenesis, the failure to clear apoptotic cells and nuclear debris is central. The molecule MOST responsible for impaired clearance of apoptotic nuclear material in SLE is:
- A Excess BAFF (B-cell activating factor) promoting autoreactive B-cell survival
- B Reduced DNase I activity in serum failing to digest extracellular chromatin
- C Complement C1q deficiency impairing opsonization of apoptotic bodies for phagocytosis ✓
- D Toll-like receptor 7 (TLR7) overactivation by self-RNA triggering plasmacytoid DC interferon production
Explanation
C1q deficiency is the strongest single-gene risk factor for human SLE (>90% of individuals with homozygous C1q deficiency develop SLE-like disease). C1q normally opsonizes apoptotic cells (via recognition of membrane-exposed phosphatidylserine and apoptotic nuclear material), facilitating their phagocytosis by macrophages and dendritic cells. Without C1q, apoptotic cells undergo secondary necrosis, releasing nuclear antigens (dsDNA, histones, nucleosomes) that become immunogenic. While BAFF excess, TLR7 overactivation, and DNase I reduction all contribute to SLE pathogenesis, impaired apoptotic clearance via C1q deficiency is the most fundamental mechanistic defect linking nuclear antigen accumulation to autoimmunity.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.