Validation of Dried Blood Spot Immunoreactive Trypsinogen as a Biomarker of Exocrine Pancreas Function in Children With Pancreas Disease.

Abstract

Radioimmunoassay (RIA)-serum trypsin serves as a pancreas function biomarker because its blood concentration correlates with duodenal trypsin output. With the unavailability of RIA tests and global availability of dried blood spot immunoreactive trypsin (DBS-IRT) testing as part of cystic fibrosis newborn-screening programs, IRT can be made accessible for routine clinical use. We aimed to validate DBS-IRT for its use as a biomarker of exocrine pancreas function in children older than the newborn age group. Analytical accuracy of DBS-IRT was evaluated in 28 children (mean [SD] age: 13 [4.5] years) with known pancreas function status and simultaneous RIA-based serum trypsin testing. Reference ranges were established based on 134 metabolically stable children. Clinical validation was performed in 164 children with well-established pancreas phenotypes. Available cross-sectional imaging was reviewed to assess for pancreas atrophy to measure acinar cell loss. Total imprecision of DBS-IRT ranged from 7.1% to 16.4%; samples were stable samples at -20C for 28 days and showed excellent correlation to RIA-serum trypsin (r = 0.95, P < 0.001). A reference range of 6.9-21.2 ng/mL was newly established. DBS-IRT replicated serum trypsin in discriminating exocrine pancreatic insufficiency (EPI) in the cystic fibrosis group with high sensitivity (90.7%; 95% CI: 79.7%-96.9%) and specificity (94.7%; 95% CI: 73.9%-99.8%). Children with pancreatitis and EPI had significantly lower median DBS-IRT level compared with those without EPI ( P = 0.01). Low DBS-IRT was associated with pancreas atrophy ( P = 0.001). DBS-IRT was successfully validated as a biomarker of exocrine pancreas function which allows its use in clinical setting, in addition to fecal elastase to determine pancreas function.