Complement Deficiency in SLE — SCE Rheumatology MCQ

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HardSLE & Antiphospholipid SyndromeComplement Deficiency in SLESCE Rheumatology

A 28-year-old woman with established SLE is clinically quiescent. Serial testing over 2 years shows a persistently low C4, including during prolonged remission, while C3 is consistently normal and anti-dsDNA is not elevated. CH50 is reduced but AH50 is normal. C1-inhibitor concentration and function and C1q are normal, and she has never had angioedema. Which underlying complement abnormality is most likely?

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Correct answer: B — Hereditary C4 deficiency

Hereditary C4 deficiency is most likely. The decisive feature is C4 remaining low independently of clinical and serological activity, with consistently normal C3. Low total C4 or C4A gene copy number can produce a fixed low baseline C4 and is associated with SLE susceptibility. Reduced CH50 with preserved AH50 localises the abnormality to the classical pathway. Factor B deficiency would impair AH50. C2 deficiency can reduce CH50 but does not itself explain a low C4 antigen concentration. Acquired C1-inhibitor deficiency may lower C4, but is contradicted by normal C1-inhibitor studies, normal C1q and the absence of angioedema. Mannose-binding lectin deficiency affects lectin-pathway initiation and does not explain persistent isolated low C4. C4A/C4B copy-number analysis or protein phenotyping may confirm the inherited abnormality.

Reference: Lintner KE et al. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases. Frontiers in Immunology. 2016;7:36. https://pubmed.ncbi.nlm.nih.gov/26913032/