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Complement Investigation — SCE Rheumatology MCQ

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HardAutoimmune SerologyComplement InvestigationSCE Rheumatology

A 45-year-old woman with systemic lupus erythematosus has been clinically quiescent for 12 months. Her anti-dsDNA titre, urinalysis and renal function are stable. Repeated, appropriately handled serum samples show a normal C3 concentration, persistently low C4 concentration and reduced total classical pathway haemolytic activity (CH50). She has no history of recurrent angioedema or invasive bacterial infection. Which additional investigation would best localise the complement abnormality?

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Correct answer: C — Measure AP50 and targeted individual classical pathway components, including C1q and C2, with confirmation of C4

The correct answer is C. Persistently low C4 with reduced CH50, despite normal C3 and clinically quiescent SLE, raises the possibility of an early classical pathway abnormality rather than uncomplicated fluctuation from active lupus. AP50 assesses whether alternative pathway function is preserved; the combination of abnormal CH50 and preserved AP50 localises dysfunction to the classical pathway. Targeted measurement or functional assessment of C1q, C2 and C4 can then identify a specific inherited or acquired abnormality. Anti-C1q antibodies may support assessment of lupus nephritis but do not localise a complement defect. C1 inhibitor testing is principally indicated for recurrent angioedema without urticaria. No further testing or repeating C3 alone would not explain the reproducible low C4 and CH50.

Reference: North West London Pathology, Pathology User Guide, Version 6.1, section 'Suggested Profiles for Immunology – Immune Deficiency', August 2025. https://www.nwlpathology.nhs.uk/wp-content/uploads/2025/09/Pathology-User-guide-V6.1.pdf