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• W4313553442 abstract "Abstract Background Hereditary angioedema (HAE) is a rare and potentially life-threatening disease. Noninvasive and disease-specific biomarkers are needed for the early diagnosis and clinical management of HAE. Objective We sought to apply untargeted proteomics profiling and targeted proteomics validation to identify pathogenic mechanisms and candidate biomarkers of HAE. Methods Data-independent acquisition (DIA)-based proteomics profiling was performed in urine samples of HAE patients and healthy controls. Bioinformatics analysis was used for functional annotation and pathway enrichment of differentially expressed proteins. Furthermore, promising biomarker candidates were validated in another independent clinical cohort using parallel reaction monitoring (PRM) targeted proteomics quantification. Results Different urinary proteomics profiles were identified among type 1 HAE, type 2 HAE and healthy controls. A total of 401 differentially expressed proteins were identified between type 1 HAE and healthy controls. Bioinformatics analysis showed that several biological processes and pathways were significantly enriched in HAE, including complement and coagulation cascades, cell adhesion molecules, immune response, proteolysis, and bradykinin catabolic process. Moreover, a promising biomarker panel (C1-INH, KNG1 and EGF) were validated in another independent clinical cohort. The area under the curve (AUC) value of this biomarker panel reached 0.910 for HAE diagnosis (sensitivity: 91.7, specificity: 88.9, P <0.001). Conclusions This study describes the first application of a DIA-PRM workflow to identify noninvasive and disease-specific biomarkers in HAE patients. These findings will contribute to the pathogenesis research and biomarker discovery of HAE. Key Messages Different urinary proteomics profiles were identified among type 1 HAE, type 2 HAE and healthy controls. Several biological processes and pathways were significantly enriched in HAE, including complement and coagulation cascades, cell adhesion molecules, immune response, proteolysis, and bradykinin catabolic process. A urinary biomarker panel (C1-INH, KNG1, and EGF) could be a promising noninvasive diagnostic tool for HAE." @default.
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• W4313553442 date "2023-01-05" @default.
• W4313553442 modified "2023-09-25" @default.
• W4313553442 title "Identification of noninvasive and disease-specific biomarkers in hereditary angioedema using urinary proteomics" @default.
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• W4313553442 doi "https://doi.org/10.1101/2023.01.03.23284171" @default.
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