In systemic lupus erythematosus (SLE), defective clearance of apoptotic cellular debris is a key upstream event driving autoimmunity. Which complement component deficiency most strongly predisposes to SLE by this mechanism?

• A C4 deficiency — C4b opsonizes apoptotic bodies for clearance by phagocytes; C4 deficiency impairs this clearance
• B C3 deficiency — C3b opsonization is the key step; complete C3 deficiency invariably causes SLE
• C C5 deficiency — terminal complement complex (MAC) is needed for lysis of apoptotic cells; C5 deficiency leads to accumulation of intact apoptotic blebs
• D C1q deficiency — C1q directly binds apoptotic cell surfaces and opsonizes debris for macrophage uptake; C1q deficiency is the strongest complement deficiency predisposing to SLE with >90% of C1q-deficient patients developing lupus-like disease ✓

Explanation

C1q binds directly to phosphatidylserine and nuclear materials exposed on the surface of apoptotic cells, acting as an opsonin that facilitates macrophage efferocytosis (phagocytic clearance of apoptotic debris). C1q deficiency is the single complement deficiency most strongly associated with SLE: >90% of patients with complete C1q deficiency develop a severe SLE-like syndrome. Without C1q, apoptotic blebs containing nuclear antigens (histones, dsDNA, snRNPs) accumulate, triggering dendritic cell activation and autoantibody generation. C4 deficiency (especially C4A null allele) is common in SLE but is less penetrant than C1q deficiency. C3 deficiency causes recurrent infections and susceptibility to immune complex disease, but is not as tightly linked to SLE as C1q. C5 deficiency predisposes to Neisseria infections.

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

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