Hereditary angioedema plasma proteomics following specific plasma kallikrein inhibition with lanadelumab

作者：Dan Sexton, Anton Kichev, Salomé Juethner, Dave Yeung, Amanda MacDonald, Ezequiel Anokian, Bin Li · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2024.1471168 · 被引用次数：7 · 研究领域：Coagulation, Bradykinin, Polyphosphates, and Angioedema、Complement system in diseases、Hemophilia Treatment and Research

Introduction Plasma proteomics analyses were performed to identify novel disease state biomarkers of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) and investigate the biological consequences of specific plasma kallikrein inhibition with lanadelumab. Methods Affinity proteomic analyses were performed using plasma from healthy controls ( n =30) and patients with HAE-C1INH before (baseline, n =125) and after 6 months of treatment with lanadelumab (300 mg every 2 weeks, n =112) using the SomaScan platform. Results Relative plasma levels for several proteins differed significantly between controls and patients with HAE-C1INH, and between matched baseline and post-treatment samples from patients with HAE-C1INH. As expected, C1 inhibitor and complement C4 were significantly lower ( P <1.10e-39 false discovery rate [fdr], P <6.6e-25 fdr, respectively) in HAE-C1INH baseline plasma versus controls. Cleaved high-molecular-weight kininogen, a biomarker of excess kallikrein-kinin system (KKS) activation, was higher in HAE-C1INH baseline plasma versus controls ( P <6.7e-6 fdr) and was reduced in HAE-C1INH plasma after lanadelumab treatment. Of 1041 identified proteins that differed significantly ( P <0.05) from controls and HAE-C1INH baseline plasma, 120 proteins were no longer different between controls and patients with HAE-C1INH after 6 months of lanadelumab treatment. Canonical pathway and local network analyses of HAE-C1INH plasma proteom...