High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality
High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality
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DOI：
10.1111/j.1365-2249.2007.03561.x
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发表时间：
2008-02-08
影响因子：
4.6
通讯作者：
Bruunsgaard, H.
中科院分区：
文献类型：
--
作者：
Johansen, J. S.;Pedersen, A. N.;Bruunsgaard, H.
YKL-40由巨噬细胞、中性粒细胞、软骨细胞、内皮细胞、血管平滑肌细胞和癌细胞分泌。在人体内研究中，白细胞介素（IL）-6刺激YKL-40的产生。高血清YKL-40与炎性疾病和癌症患者的不良预后相关。我们研究了血清YKL-40是否与相对健康的80岁老年人的系统性低水平炎症、免疫风险表型和死亡率相关。通过酶联免疫吸附试验（ELISA）测定了151名老年人血清YKL-40、IL-6和肿瘤坏死因子（TNF）-α，并测定了89名18-30岁青年人血清YKL-40。在6年的随访中，51名老年人死亡。老年人血清YKL-40水平高于年轻人（中位数116对31 μ g/l，P < 0.0005）。在老年女性（斯皮尔曼rho = 0.30，P = 0.009）和男性（rho = 0.25，P = 0.003）中，血清YKL-40与血清IL-6相关，但在老年女性中仅与血清TNF-α（rho = 0.23，P = 0.05）和C-反应蛋白（CRP）（rho = 0.57，P < 0.0005）相关。此外，高血清YKL-40水平与低CD 4：CD 8细胞比率相关。血清YKL-40的单变量分析（经数学转换并除以三分位数）显示与全因死亡率显著相关[三分位数3：风险比（HR）= 2.38，95%置信区间（CI）：1.19-4.78，P = 0.02]。在调整潜在混杂因素（性别、吸烟、体重指数、慢性病和抗炎药）后，该效应持续存在。这些结果表明，血清YKL-40是老年人全因死亡率的预后和敏感的生物标志物。
YKL-40 is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle- and cancer cells. Interleukin (IL)-6 stimulates YKL-40 production in human in vivo studies. High serum YKL-40 is associated with poor prognosis in patients with inflammatory diseases and cancer. We studied whether serum YKL-40 was associated with systemic low-level inflammation, an immune risk phenotype, and mortality in relatively healthy 80-year old humans. Serum YKL-40, IL-6 and tumour necrosis factor (TNF)-alpha were measured by enzyme-linked immunosorbent assays (ELISAs) in octogenarians (n = 151) and serum YKL-40 in 18-30-year-olds (n = 89). Fifty-one of the octogenarians died during the 6-year follow-up. Serum YKL-40 in octogenarians was higher compared to the level in young people (median 116 versus 31 mu g/l, P < 0.0005). Serum YKL-40 correlated with serum IL-6 in elderly women (Spearman's rho = 0.30, P = 0.009) and men (rho = 0.25, P = 0.003), but only with serum TNF-alpha (rho = 0.23, P = 0.05) and C-reactive protein (CRP) (rho = 0.57, P < 0.0005) among the elderly women. In addition, high serum level of YKL-40 was associated with a low CD4 : CD8 cell ratio. Univariate analysis of serum YKL-40 (logarithmically transformed and divided by tertiles) showed significant association with all-cause mortality [tertile 3: hazard ratio (HR) = 2.38, 95% confidence interval (CI): 1.19-4.78, P = 0.02]. The effect persisted after adjusting for potential confounders (sex, smoking, body mass index, chronic disease and anti-inflammatory medicine). These results suggest that serum YKL-40 is a prognostic and sensitive biomarker of all-cause mortality in octogenarians.