Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET Cohort

Blood Adv. 2024 Apr 9:bloodadvances.2023011388. doi: 10.1182/bloodadvances.2023011388. Online ahead of print.ABSTRACTInhibitor development is the most severe complication of hemophilia A care, and is associated with increased morbidity and mortality. The aim of this study was to use a novel IgG epitope mapping method to explore the factor VIII (FVIII)-specific epitope profile in the SIPPET cohort population and to develop an epitope-mapping based inhibitor prediction model. The population consisted of 122 previously untreated patients with severe hemophilia A that were followed-up for 50 days of exposure to FVIII or 3 years, whichever occurred first. Sampling was performed before FVIII treatment and at the end of the follow-up. The outcome was inhibitor development. The FVIII epitope repertoire was assessed by means of a novel random peptide phage-display assay. A LASSO regression model and a random forest model were fitted on post-treatment sample data and validated in pre-treatment sample data. The predictive performance of these models was assessed by the C-statistic and a calibration plot. We identified 27,775 peptides putatively directed against FVIII, which were used as input for the statistical models. The C-statistic of the LASSO and random forest models were good at 0.78 (95%CI: 0.69-0.86) and 0.80 (95%CI: 0.72-0.89). Model calibration of both models was moderately good. Two statistical models, developed on data from a novel random peptide phage display assay, were u...
Source: Adv Data - Category: Epidemiology Authors: Source Type: research