Establishment of reference intervals for soluble ST2 from a United States population

Soluble ST2 (sST2) is a protein in the interleukin-1 receptor family secreted by myocytes in response to mechanical strain. Elevated sST2 is strongly prognostic in patients with heart failure. sST2 was measured using the Presage™ ST2 ELISA. Evaluation included imprecision, linearity, recovery, analytical sensitivity, limit of quantification, stability, and sample type comparisons. Gender-specific reference intervals were established from 245 male and 245 female serum specimens. At sST2 concentrations of 11.6, 26.9, and 88.0 ng/mL, the within-day CV was 7.6, 2.4, and 3.8%, respectively and the total CV was 11.5, 14.0, and 6.3%, respectively. The assay was linear over a concentration range of 2.8–161.1 ng/mL (y = 0.95x + 2.25; R 2 = 0.997; Sy.x = 3.03). The limit of quantification was 3.3 ng/mL. sST2 was stable for 2 days at room temperature, 10 days at 4 °C, and 30 days at −20 °C. Concentrations of sST2 were significantly higher in males compared to females (24.9 vs. 16.9 ng/mL; p < 0.0001) but were not correlated by age in either gender (r = −0.07; p = 0.14). Reference intervals for sST2 were determined to be 8.6–49.3 and 7.2–33.5 ng/mL for males and females, respectively. The Presage™ ST2 ELISA had acceptable performance characteristics for quantifying sST2 in serum or plasma. The assay is precise and linear over a wide sST2 concentration range and can measure low sST2 concentrations. Concentrations of sST2 are unaffected by age but are higher in males compared to females.