Leukocyte proteomics coupled with serum metabolomics identifies novel biomarkers and abnormal amino acid metabolism in Kawasaki disease
Leukocyte proteomics coupled with serum metabolomics identifies novel biomarkers and abnormal amino acid metabolism in Kawasaki disease
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白细胞蛋白质组学与血清代谢组学相结合，鉴定出川崎病的新型生物标志物和异常氨基酸代谢
DOI：
10.1016/j.jprot.2021.104183
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发表时间：
2021
影响因子：
3.3
通讯作者：
Lv Haitao
中科院分区：
文献类型：
--
作者：
Qian Guanghui;Xu Lei;Qin Jie;Huang Hongbiao;Zhu Liyan;Tang Yunjia;Li Xuan;Ma Jin;Ma Yingying;Ding Yueyue;Lv Haitao
川崎（KD）是一种可导致严重心血管并发症的系统性血管炎，而特异性生物标志物的开发和临床应用可能有助于KD的诊断和避免某些并发症。为此，首先通过白细胞蛋白质组学和血清代谢组学分析研究了急性KD伴冠状动脉病变（CAL）患者的分子谱。与健康对照组相比，在急性KD患者中共鉴定了269种差异丰富的蛋白质和35种差异丰富的代谢物，其水平变化倍数最高。其中，进一步分析了指示KD进展的几种非常有希望的候选标志物蛋白和代谢物，例如增加的蛋白ALPL、NAMPT和S100 P，以及减少的蛋白C1 QB和载脂蛋白家族成员。此外，代谢物，包括琥珀酸，dGMP，透明质酸，L-色氨酸，丙酰肉毒碱，肌苷，磷酸胆碱，被发现是高度准确的KD患者和健康对照之间的区别。有趣的是，急性KD患者中一组不同的蛋白质和代谢物的异常表达水平可以在静脉内免疫球蛋白（IVIG）治疗后恢复到正常水平。总体而言，这项工作揭示了新的生物标志物和异常的氨基酸代谢作为一个突出的特点，参与KD患者CAL。SignificanceKD是经常伴随着危及生命的冠状动脉血管炎的发展。在这里，白细胞蛋白质组学和血清代谢组学在急性KD患者与CAL的配置文件进行了首次调查，这里确定的几个枢纽分子可以用作KD诊断的补充生物标志物。此外，代谢组学异常尤其是氨基酸在KD患者中尤为突出。有趣的是，急性KD患者中一组不同的蛋白质和代谢物的异常表达水平可以在IVIG治疗后恢复到正常水平。因此，这些发现可能有助于理解IVIG活性以及IVIG抵抗患者的潜在机制，从而为探索KD相关机制提供新的视角。
Kawasaki disease (KD) is a systemic vasculitis that can lead to severe cardiovascular complications, whereas the development and clinical usage of specific biomarkers might help diagnose KD and avoid certain complications. To this end, the molecular profiles of acute KD patients with coronary artery lesions (CAL) were first investigated through leukocyte proteomics and serum metabolomics assays. A total of 269 differentially abundant proteins and 35 differentially abundant metabolites with the top fold-changed levels were identified in acute KD patients compared to those in the healthy controls. Among them, several highly promising candidate marker proteins and metabolites indicative of KD progression were further analysed, such as the increased proteins ALPL, NAMPT, and S100P, as well as the decreased proteins C1QB and apolipoprotein family members. Moreover, metabolites, including succinic acid, dGMP, hyaluronic acid, L-tryptophan, propionylcarnitine, inosine, and phosphorylcholine, were found to be highly accurate at distinguishing between KD patients and healthy controls. Interestingly, the abnormal expression levels of a distinct set of proteins and metabolites in acute KD patients can be restored to normal levels upon intravenous immunoglobulin (IVIG) treatment. Overall, this work has revealed novel biomarkers and abnormal amino-acid metabolism as a prominent feature involved in KD patients with CAL.SignificanceKD is frequently concomitant with the development of life-threatening coronary vasculitis. Here, the profiles of leukocyte proteomics and serum metabolomics in acute KD patients with CALs were first investigated, and several hub molecules identified here could be used as supplemental biomarkers for KD diagnosis. Moreover, the metabolomic abnormalities especially the amino acids are particularly prominent in KD patients. Interestingly, the abnormal expression levels of a distinct set of proteins and metabolites in acute KD patients can be restored to normal levels upon IVIG treatment. Therefore, these findings might help understand the IVIG activities and also the underlying mechanisms of IVIG-resistant patients, thereby providing a new perspective for the exploration of mechanisms related to KD.