Development and analytical performance of a new ARCHITECT automated dipeptidyl peptidase-4 immunoassay

摘要

Background Dipeptidyl peptidase-4 (DPP-4) may be a suitable biomarker to identify people with severe asthma who have greater activation of the interleukin-13 (IL-13) pathway and may therefore benefit from IL-13-targeted treatments. We report the analytical performance of an Investigational Use Only immunoassay and provide data on the biological range of DPP-4 concentrations. Methods We assessed assay performance, utilising analyses of precision, linearity and sensitivity; interference from common endogenous assay interferents, and from asthma and anti-diabetic medications, were also assessed. The assay was used to measure the range of serum DPP-4 concentrations in healthy volunteers and subjects with diabetes and severe, uncontrolled asthma. Results The total precision of DPP-4 concentration measurement (determined using percentage coefficient of variation) was ≤5% over 20 days. Dilution analysis yielded linear results from 30 to 1305ng/mL; the limit of quantitation was 19.2ng/mL. No notable endogenous or drug interferences were observed at the expected therapeutic concentration. Median DPP-4 concentrations in healthy volunteers and subjects with asthma or Type 1 diabetes were assessed, with concentrations remaining similar in subjects with diabetes and asthma across different demographics. Conclusion These analyses indicate that the ARCHITECT DPP-4 Immunoassay is a reliable and robust method for measuring serum DPP-4 concentration. Graphical abstract Display Omitted Highlights ? DPP-4 may be a suitable biomarker for identifying people with IL-13-driven asthma. ? The new automated DPP-4 immunoassay is performed on the ARCHITECT i System. ? This Investigational Use Only assay reliably measures serum DPP-4 concentrations. ? This assay could be used to identify subjects who might respond to tralokinumab. ? This assay is being utilised in Phase III severe asthma studies of tralokinumab.