Fig 1: FXII W268R activates the kallikrein–kinin pathway.a Citrate plasma of affected (n = 3) and healthy family members (n = 3) was immunoblotted for prekallikrein (PK) showing substantial cleavage of PK (black arrow) to kallikrein (red arrow), n = 2 technical replicates. This corresponds to reduced PK activity (b) and plasma levels (c) in affected individuals (n = 3 affected vs. n = 3 healthy). d FXIIa-C1-inhibitor (FXIIa-C1-INH) and e) PK-C1-INH complexes in patient plasma (n = 3 affected vs. n = 3 healthy). f Citrate plasma of affected (n = 3) and healthy family members (n = 3) was immunoblotted for high-molecular-weight kininogen (HMWK) showing its complete degradation (black arrow) to cleaved HMWK (cHMWK) (red arrow), n = 2 technical replicates. Correspondingly, increased cHMWK activity (g) and bradykinin plasma levels (h) (n = 3 affected vs. n = 3 healthy; n = 2 affected vs. n = 7 healthy and n = 2 HAE I/II) are detectable in the plasma of affected patients. PK and cHMWK activity were measured by chromogenic assays, PK and bradykinin plasma levels were assessed by ELISA. Graphs show individual data points and the mean ± s.e.m. Statistical significance is indicated by unpaired Student’s t test with Welch’s correction (b, c, d, e, g) or one-way ANOVA with Sidak’s multiple comparisons test (h). Source data are provided as a source data file.