Abstract
Rationale: Serum periostin has been proposed as a systemic biomarker of IL-13 pathway activation in the lung. We developed an investigational use only (IUO) immunoassay to detect serum periostin on the ARCHITECT® immunoassay iSystem.
Methods: The ARCHITECT® Periostin assay is a two-step immunoassay for quantitative determination of periostin in human serum using Chemiluminescent Magnetic Immunoassay (CMIA) technology. Periostin is captured by microparticles coated with an anti-periostin monoclonal antibody (mAb). After incubation and washing, a second anti-periostin mAb conjugated with acridinium is added, chemiluminesence is triggered, and signal is measured as relative light units (RLUs). Amount of periostin present and RLUs detected are directly correlated. ARCHITECT®iSystem has 200 tests per hour throughput. The analytical performance of the assay was assessed.
Results: A sandwich immunoassay format was optimized for robust analytical performance. Five-day precision results were <6.4 %CV across 3 controls and 3 serum based panels. Limit of quantitation was ≤4 ng/mL. Specimen dilution analysis yielded linear results across the assay dynamic range (4-100 ng/mL). No endogenous sample and drug interferences were observed. All known lung periostin isoforms were detected. Using this newly developed IUO assay, we measured periostin levels in >1000 serum samples from patients with severe asthma. The range was 5.2-73.3 ng/mL and median periostin level was 16.44 ng/mL.
Conclusions: The IUO ARCHITECT® Periostin immunoassay is a reliable and robust test to measure serum periostin levels. The assay is being used in ongoing Phase 3 trials of tralokinumab, a human IgG4 mAb that neutralizes IL-13.
- Copyright ©ERS 2015