CAPS sera activate complement and induce C5b-9 deposition. (A) Sera from a representative patient with CAPS (CAPS5) induced C5b-9 deposition on PIGA⁻ TF-1 cells. C5b-9 deposition was blocked by eculizumab (a C5 inhibitor) and partially by the factor D inhibitor ACH-4471. The mHam assay also showed a positive result (>20% nonviable cells) with CAPS sera, which was attenuated by eculizumab and a factor D inhibitor. (B) mHam was negative (>20% cell killing) when the patient was tested at steady state and positive when tested during acute CAPS. Patient CAPS5 had a CR1 V1675L variant; NHS, normal human serum; NHS(H), heat-inactivated NHS; Stx1, Shiga toxin 1 (positive control); SSC, side scatter; anti-C5 Ab, eculizumab; and ACH-4471, factor D inhibitor.