Parallel comparison of three methodologies for measuring functional C1-inhibitor in Hereditary angioedema patients
| Autor: | Archana Kapoor, Brijesh K. Garg, Priya S. Chockalingam, Peng Lu, Zhiwei Zhou |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Immunology Sensitivity and Specificity Gastroenterology C1-inhibitor 03 medical and health sciences 0302 clinical medicine Double-Blind Method Internal medicine medicine Humans Immunology and Allergy Immunoassay Pharmacology Cross-Over Studies medicine.diagnostic_test biology Receiver operating characteristic Chromogenic business.industry Angioedemas Hereditary Curve analysis Kallikrein Placebo Effect bacterial infections and mycoses medicine.disease 030104 developmental biology Chromogenic Compounds ROC Curve 030220 oncology & carcinogenesis Pharmacodynamics Hereditary angioedema Disease Progression biology.protein Female business Complement C1 Inhibitor Protein |
| Zdroj: | International Immunopharmacology. 81:106348 |
| ISSN: | 1567-5769 |
| Popis: | Hereditary angioedema (HAE) types I and II are characterized by functional C1 inhibitor (fC1-INH) deficiency which results in bradykinin overproduction. Sensitive, specific and robust methods to quantitate fC1-INH in human samples are required for diagnosing HAE and/or to measure pharmacodynamic activity of C1-INH drugs in clinical studies. To date, three methods have been reported in literature to measure fC1-INH: conventional chromogenic assay measuring residual C1-esterase activity, and immunoassays based on functional binding to either activated complement C1s or Factor XIIa/kallikrein. We used three qualified/validated fit-for purpose methods to quantitate fC1-INH in human plasma and to conduct a parallel comparison for diagnostic purposes and as a read-out for pharmacodynamic activity. Sensitivity and specificity were determined from the Receiver Operator Characteristics (ROC) curve analysis of the three fC1-INH methods through testing of fifty healthy control vs. HAE plasma samples. fC1-INH profile of fifteen HAE subjects, who underwent different treatment regimen in a cross-over Shire C1-INH clinical study, was analyzed in these three methods in parallel. A correlation analysis performed between these methods using data generated from clinical samples showed that profiles obtained from different fC1-INH methods matched for individual HAE subjects. Our findings suggest that functional binding immunoassay methods serve as reliable alternates for conventional chromogenic method to quantitate fC1-INH in human plasma samples with a better dynamic range of detection and ease of use. Of the two immunoassays used in this study, FXIIa-binding method gave better sensitivity, specificity, and correlation to the chromogenic method as a diagnostic method to distinguish HAE samples from healthy controls. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect