Neutrophil-derived lipocalin-2 in adult-onset Still's disease: a novel biomarker of disease activity and liver damage.
Neutrophil-derived lipocalin-2 in adult-onset Still's disease: a novel biomarker of disease activity and liver damage.
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DOI：
10.1093/rheumatology/keaa368
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发表时间：
2021-01-05
期刊：
影响因子：
--
通讯作者：
Hu Q
中科院分区：
文献类型：
--
作者：
Jia J;Yang L;Cao Z;Wang M;Ma Y;Ma X;Liu Q;Teng J;Shi H;Liu H;Cheng X;Ye J;Su Y;Sun Y;Chi H;Liu T;Wang Z;Wan L;Yang C;Hu Q
肝损伤是一种常见的表现，在成人发病的斯蒂尔病（AOSD）中可能危及生命，这是一种自身炎症性疾病。AOSD的标志是中性粒细胞的活化，其在肝脏中的浸润被怀疑促进组织损伤。在这里，我们的目的是确定一个候选的生物标志物，并验证其与AOSD肝损伤的相关性。对来自未经治疗的活动性AOSD患者和健康供体的中性粒细胞进行转录组分析。在AOSD的中性粒细胞、血浆和肝活检中评估脂质运载蛋白-2（LCN 2）表达。分析LCN 2与不同变量的相关性及其对AOSD患者肝损害的识别能力。通过RNA测序发现肝脏炎症中的新生物标志物LCN 2在AOSD中性粒细胞中上调，并在mRNA和蛋白质水平上得到证实。AOSD患者血浆LCN 2水平显著高于健康对照组、RA和SLE患者。血浆LCN 2水平与炎症标志物、全身评分、HScore和细胞因子密切相关。此外，LCN 2水平在伴有肝脏受累的活动性AOSD中升高，并与肝功能障碍独立相关。在3例持续性肝损伤患者的肝活检组织中检测到LCN 2表达增强。此外，用于鉴别AOSD与其他肝脏疾病的肝损伤的LCN 2曲线下面积值为0.9694。我们的研究结果表明，在AOSD患者的血浆和肝组织中，嗜酸性粒细胞衍生的LCN 2高于健康对照，它可以作为一个有效的生物标志物，用于识别AOSD与全身炎症，特别是由过度炎症引起的肝损伤。
Liver damage is a common manifestation and can be life-threatening in adult-onset Still’s disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation.
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影响因子：
4.4
作者：
Jamilloux, Yvan;Gerfaud-Valentin, Mathieu;Seve, Pascal
通讯作者：
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影响因子：
13.3
作者：
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通讯作者：
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影响因子：
13.6
作者：
Govoni, Marcello;Bortoluzzi, Alessandra;Modena, Vittorio
通讯作者：
Modena, Vittorio
Lipocalin-2/ngal作为炎症和代谢疾病的生物标志物的潜力。
DOI：
10.3109/1354750x.2015.1123354
发表时间：
2015
期刊：
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
影响因子：
--
作者：
Abella V;Scotece M;Conde J;Gómez R;Lois A;Pino J;Gómez-Reino JJ;Lago F;Mobasheri A;Gualillo O
通讯作者：
Gualillo O
影响因子：
12.8
作者：
Mahroum, Naim;Mahagna, Hussein;Amital, Howard
通讯作者：
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