Laboratory of Molecular Medicine, Department of Clinical Immunology 7631, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Immunobiology. 2013 Oct;218(10):1227-34. doi: 10.1016/j.imbio.2013.04.010. Epub 2013 Apr 24.
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.
YKL-40 来源于 CHI3L1 基因，与感染和炎症性疾病的预后相关。我们假设血浆 YKL-40 浓度和 CHI3L1 基因型可作为全身炎症反应综合征（SIRS）和脓毒症评估的预后生物标志物。本研究的目的是评估 SIRS 和脓毒症患者血浆 YKL-40 和 CHI3L1 基因型的预后价值。在入住重症监护病房（ICU）时分析了血浆 YKL-40 和 CHI3L1 基因型（rs4950928），在连续 SIRS 患者的两个前瞻性队列中（队列 1，n=272；队列 2，n=502）进行了分析。通过接受者操作特征分析确定了队列 1 中预测生存的血浆 YKL-40 截止值，并在队列 2 中进行了验证。在队列 1 中，血浆 YKL-40≤505ng/ml 的患者（曲线下面积 0.64（95%置信区间 0.57-0.70），p<0.001，敏感性 53%，特异性 76%）第 90 天生存情况更好（81%比 55%，p<0.001，危险比（HR）2.29（95%CI 1.29-4.07））。在第二队列中，血浆 YKL-40≤505ng/ml 也与更高的生存率相关（61%比 38%，p<0.001，HR 1.43（1.03-1.99））。CHI3L1 次要等位基因纯合性与入住 ICU 时的低血浆 YKL-40 相关（p=0.002），在 ICU 入住的前 14 天内浓度没有变化（p=0.462），但与生存改善无关。总之，SIRS 和脓毒症患者入住 ICU 时的血浆 YKL-40≤505ng/ml 与生存改善相关。然而，对于 CHI3L1 等位基因低表达 YKL-40 的纯合子患者，并未观察到这种关联。
