Sejersen Kristina, Mandic Havelka Aleksandra, Lipcsey Miklos, Larsson Anders
Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
Section of Clinical Chemistry, Unilabs Laboratory Medicine Stockholm, Solna, Sweden.
Scand J Clin Lab Invest. 2025;85(4):299-304. doi: 10.1080/00365513.2025.2512997. Epub 2025 Jun 2.
Calprotectin is a 24 kD heterodimer of calcium-binding proteins S100A8 and S100A9. At present, there is a lack of knowledge about the specificity of various methods for calprotectin detection, whether they measure only dimers between S100A8 and S100A9, S100A8-S100A8 dimers, S100A9/S100A9 dimers, or free subunits. This study aimed to compare total calprotectin levels with those of its subunits, S100A8 and S100A9, in ICU patients. This prospective observational study includes 271 sepsis and non-sepsis patients. Inclusion criteria were admission to intensive care and the presence or need for an arterial catheter. Plasma total calprotectin was measured at ICU admission and the following two days by particle-enhanced turbidimetric (PETIA) calprotectin reagents from Gentian AS and a Mindray BS380 chemistry analyzer. S100A8 and S100A9 were analyzed by commercial sandwich ELISA DY4570-05, and DY5578, R&D Systems, respectively. Sepsis was defined according to Sepsis-3 as suspected infection and a Sequential organ failure assessment (SOFA) >2 on admission. Receiver operating characteristic (ROC) analysis showed that total calprotectin had a larger area under the curve (AUC) for distinguishing sepsis from non-sepsis patients (0.67) compared to S100A8 (0.59) and S100A9 (0.52). For predicting 30-day mortality, S100A9 had a higher AUC value (0.64) than S100A8 (0.59). However, weak correlations between total calprotectin and its subunits suggest no significant predictive relationship for 30-day mortality, while also highlighting potential assay harmonization challenges across manufacturers.
钙卫蛋白是一种由钙结合蛋白S100A8和S100A9组成的24kD异二聚体。目前,对于各种钙卫蛋白检测方法的特异性尚缺乏了解,这些方法是仅测量S100A8和S100A9之间的二聚体、S100A8 - S100A8二聚体、S100A9/S100A9二聚体,还是游离亚基。本研究旨在比较重症监护病房(ICU)患者中总钙卫蛋白水平与其亚基S100A8和S100A9的水平。这项前瞻性观察性研究纳入了271例脓毒症和非脓毒症患者。纳入标准为入住重症监护病房且存在或需要动脉导管。在ICU入院时及随后两天,使用来自Gentian AS的颗粒增强比浊法(PETIA)钙卫蛋白试剂和迈瑞BS380化学分析仪测量血浆总钙卫蛋白。分别使用R&D Systems公司的商用夹心ELISA DY4570 - 05和DY5578分析S100A8和S100A9。根据Sepsis - 3,脓毒症定义为疑似感染且入院时序贯器官衰竭评估(SOFA)>2。受试者操作特征(ROC)分析表明,与S100A8(0.59)和S100A9(0.52)相比,总钙卫蛋白在区分脓毒症患者和非脓毒症患者方面具有更大的曲线下面积(AUC)(0.67)。对于预测30天死亡率,S100A9的AUC值(0.64)高于S100A8(0.59)。然而,总钙卫蛋白与其亚基之间的弱相关性表明,对于30天死亡率不存在显著的预测关系,同时也凸显了不同制造商之间潜在的检测方法协调挑战。