{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:40:33Z","timestamp":1777480833683,"version":"3.51.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceuticals U.S.A.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Affinity proteomic analyses were performed using plasma from healthy controls (<jats:italic>n<\/jats:italic>=30) and patients with HAE-C1INH before (baseline, <jats:italic>n<\/jats:italic>=125) and after 6 months of treatment with lanadelumab (300 mg every 2 weeks, <jats:italic>n<\/jats:italic>=112) using the SomaScan platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (<jats:italic>P<\/jats:italic>&amp;lt;1.10e-39 false discovery rate [fdr], <jats:italic>P<\/jats:italic>&amp;lt;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 (<jats:italic>P<\/jats:italic>&amp;lt;6.7e-6 fdr) and was reduced in HAE-C1INH plasma after lanadelumab treatment. Of 1041 identified proteins that differed significantly (<jats:italic>P<\/jats:italic>&amp;lt;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 proteomics suggest dysregulation in KKS, coagulation, cell adhesion, and connective tissue degradation that approach that of healthy controls following treatment with lanadelumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Proteomic analyses of plasma from patients with HAE-C1INH before and after treatment with lanadelumab compared with healthy controls confirmed known HAE-C1INH biomarkers and identified additional potential biomarkers of plasma kallikrein dysregulation for further investigation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1471168","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T04:10:57Z","timestamp":1746763857000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hereditary angioedema plasma proteomics following specific plasma kallikrein inhibition with 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