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Park, Ji, Kim, Moon, Hur, and Yun: Establishing Reference Intervals for Soluble ST2 Assay in a Korean Population
Original Article

Lab Med Online 2017;7(4):176-181.

Published online: 17 October 2017

DOI: https://doi.org/10.3343/lmo.2017.7.4.176

Establishing Reference Intervals for Soluble ST2 Assay in a Korean Population

Mikyoung Park, M.D.1, Misuk Ji, M.D.2, Hanah Kim, M.D.1, Hee-Won Moon, M.D.1, Mina Hur, M.D.1, Yeo-Min Yun, M.D.1,

1Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea

2Department of Laboratory Medicine, VHS Medical Center, Seoul, Korea

Corresponding author: Yeo-Min Yun Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea Tel: +82-2-2030-5582, Fax: +82-2-2030-5587, E-mail: ymyun@kuh.ac.kr

Received 19 October 201620 April 2017       Accepted 21 April 2017

Copyright © 2017 The Korean Society for Laboratory Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Soluble ST2 (sST2) has emerged as a biomarker of heart failure. Previous studies indicated 35 ng/mL of sST2 as the clinically prognostic cutoff value. This study aims to establish reference intervals in a Korean population using an sST2 assay and to evaluate the applicability of the cutoff value.

Methods

From March to May 2014, sST2 levels were assayed in serum samples of 255 cardio-healthy Koreans (128 men and 127 women) using the Presage ST2 ELISA kit (Critical Diagnostics, USA). The reference interval for sST2 was defined using the nonparametric percentile method according to the CLSI EP28-A3c guideline.

Results

The median sST2 concentrations were 23.8 ng/mL (interquartile range (IQR), 19.0-28.7), 26.6 ng/mL (IQR, 21.0-30.9), and 21.9 ng/mL (IQR, 17.3-26.5) for the entire cohort, men, and women, respectively. sST2 levels were significantly higher in men than in women (P<0.0001). The 97.5th percentile upper reference limits for sST2 were 43.8 ng/mL, 49.6 ng/mL, and 35.4 ng/mL for the cohort, men, and women, respectively. Gender-specific upper reference limits were similar to limits reported by other studies.

Conclusions

We suggest that gender-specific reference intervals should be used for the Korean population, as application of a single cutoff value of 35 ng/mL may be overcautious of the possibility of false positivity, especially in men.

Keywords: Soluble ST2, Reference interval, Korean, Heart failure

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Fig. 1.
Distributions of sST2 concentrations and reference intervals measured by the Presage ST2 ELISA kit in the entire cohort (A), males (B), and females (C). Dotted lines represent the 2.5th percentile and 97.5th percentile limits. Abbreviations: sST2, soluble suppression of tumorigenicity 2; CI, confidence interval; ELISA, enzyme-linked immunosorbent assay.
lmo-7-176f1.tif
Table 1.
Comparison of previously reported sST2 reference intervals with values from the Presage ST2 ELISA assay∗
Reference Sample size Age (yr) Specimen Unit Median sST2 (sex)† Reference intervals
Total Male Female
Dieplinger et al. [8] N (M)=338 18-64 Plasma U/mL 13 (M)‡ Not reported 4.0-31.0 2.0-21.0
  N (F)=190 18-64     8 (F)‡      
Lu et al. [4] N (M)=245 N (F)=245 18-84 18-84 Plasma ng/mL 24.9 (M)§ 16.9 (F)§ Not reported 8.6-49.3 7.2-33.5
Coglianese et al. [9]ll N (M)=462 35-74 Plasma, ng/mL Not available Not reported 10.6-13.2 (2.5th, E) 9.3-10.4 (2.5th, E)
  N (F)=674 35-74 serum       43.3-47.6 (97.5th, E) 10.3-13.1 (2.5th, Q) 30.7-45.1 (97.5th, E) 9.6-10.2 (2.5th, Q)
              44.6-46.5 (97.5th, Q) 29.4-35.3 (97.5th, Q)
Manufacturer [5] N (M)=245 18-84 Plasma, ng/mL 23.6 (M) 1.75-34.3 8.5-49.3 7.1-33.5
  N (F)=245 18-84 serum   16.2 (F) 18.8 (T)      
Present study N (M)=128 18-70 Serum ng/mL 26.6 (M) 12.6-43.8 13.4-49.6 12.1-35.4
  N (F)=127 18-70     21.9 (F) 23.8 (T)      

∗ All reference intervals were calculated using a non-parametric percentile method (95%, double sided.) except in only one study [9].

† Median sST2 values were presented except in one study [4].

‡ Median sST2 values were significantly different according to sex (Mann-Whitney U test, P <0.001).

§ Mean sST2 concentrations in the male group were significantly higher compared to that in the female group (P <0.0001).

ll Reference intervals according to sex and age was estimated using both empirical and quantile regression methods from a healthy reference sample in the Framingham Heart Study [9].

Abbreviations: sST2, soluble suppression of tumorigenicity 2; ELISA, enzyme-linked immunosorbent assay; M, males; F, females; T, total; E, empirical reference limits; Q, quantile regression reference limits.

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