In systemic lupus erythematosus, aberrant clearance of apoptotic cells is a key mechanism generating nuclear autoantigens. Which complement pathway deficiency is most strongly associated with susceptibility to SLE?

• A C3 deficiency, preventing membrane attack complex formation
• B Mannose-binding lectin (MBL) deficiency reducing lectin pathway function
• C Properdin deficiency impairing alternative pathway amplification
• D C1q deficiency, impairing opsonization and clearance of apoptotic debris ✓

Explanation

C1q is the strongest genetic risk factor for SLE among complement deficiencies; >90% of individuals with complete C1q deficiency develop lupus-like disease. C1q binds apoptotic cell surfaces and promotes their engulfment by phagocytes; without C1q, apoptotic debris accumulates, nuclear autoantigens (dsDNA, histones, snRNPs) are released, and anti-nuclear antibody responses develop. C3 deficiency leads to severe infections. MBL deficiency confers modest SLE susceptibility.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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