Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis-experience from two prospective cohorts

Abstract

YKL-40, derived from the CHI3L1 gene, has been associated with outcome of infectious and inflammatory diseases. We hypothesized that plasma YKL-40 concentrations and CHI3L1 genotype could be used as prognostic biomarkers in the assessment of systemic inflammatory response syndrome (SIRS) and sepsis. The objective of the study was to assess the prognostic value of plasma YKL-40 and CHI3L1 genotype in patients with SIRS and sepsis. Plasma YKL-40 and CHI3L1 genotype (rs4950928) were analyzed at time of admission to intensive care units (ICU), in two prospective cohorts of consecutive SIRS patients (cohort 1, n=272; cohort 2, n=502). The plasma YKL-40 cut-off for predicting survival was determined in cohort 1 by receiver operator characteristic analyses and validated in cohort 2. In cohort 1 patients with plasma YKL-40 ≤505ng/ml (area under the curve 0.64 (95% confidence interval (CI) 0.57-0.70), p<0.001, sensitivity 53%, specificity 76%) had superior day 90 survival (81% vs. 55%, p<0.001, hazard ratio (HR) 2.29 (95% CI 1.29-4.07)). In the second cohort plasma YKL-40 ≤505ng/ml was also associated with superior survival (61% vs. 38%, p<0.001, HR 1.43 (1.03-1.99)). CHI3L1 minor allele homozygosity was associated with low plasma YKL-40 at time of admission (p=0.002) and no variation (p=0.462) in concentrations throughout the first 14 days in the ICU, but this was not associated with better survival. In conclusion patients with SIRS and sepsis, plasma YKL-40 ≤505ng/ml at time of ICU admission was associated with better survival. However, this association was not observed for patients homozygous for the low expressing YKL-40 CHI3L1 allele.

Keywords: Biomarker; CHI3L1; CI; CRP; CV; Genotype; HR; ICU; INF-γ; IQR; PCT; ROC; SAPS2; SEM; SIRS; SNP; Sepsis; Systemic inflammatory response syndrome; VEGF; YKL-40; c reactive protein; chitinase-3-like-1 protein; coefficient of variations; confidence interval; hazard ratio; intensive care unit; inter quartile range; interferon γ; procalcitonin; receiver-operator characteristic; simplified acute physiology score 2; single nucleotide polymorphism; standard error of the mean; systemic inflammatory response syndrome; vascular endothelial growth factor.