In systemic lupus erythematosus (SLE), defective clearance of apoptotic cells is a key pathogenic mechanism. Which complement protein deficiency is most strongly linked to the development of SLE, and why?
- A C1q deficiency; C1q normally opsonizes apoptotic blebs for phagocytosis ✓
- B C3 deficiency; prevents opsonization of apoptotic cell debris
- C C5 deficiency; terminal complement pathway needed to lyse apoptotic cells
- D Factor D deficiency; alternative pathway needed to tag nuclear antigens
Explanation
C1q deficiency carries the highest risk for SLE among all complement deficiencies, with approximately 90% of C1q-deficient individuals developing an SLE-like syndrome. C1q normally binds to apoptotic blebs (especially surface-exposed phosphatidylserine and nuclear components) and opsonizes them for phagocytosis by macrophages. Without C1q-mediated opsonization, apoptotic cells accumulate in tissues, undergo secondary necrosis, and release nuclear antigens (histones, DNA, snRNPs), which drive autoantibody production. C1q also directly engages DNase I on the apoptotic cell surface, facilitating nuclear antigen clearance.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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