In hereditary angioedema due to C1 esterase inhibitor deficiency, which laboratory finding is typically decreased?

• A. C4
• B. C3
• C. IgE
• D. C1q

Answer: (A)

Unregulated activation of the classical complement pathway due to C1 esterase inhibitor deficiency drives consumption of C4. Normally, C1 esterase inhibitor keeps C1r and C1s in check (and also dampens the kallikrein-kinin system). When it's deficient, C1 becomes overactive, leading to continuous cleavage of C4 to C4a and C4b and thus lowering the amount of circulating C4. This low C4 is a hallmark lab finding in hereditary angioedema due to C1-INH deficiency. C1q is typically normal, which helps distinguish this from acquired angioedema (where C1q can be low). C3 is usually not markedly decreased because C3 downstream consumption is less pronounced. IgE is not involved in this mechanism.