Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province 215025, China.
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province 215025, China.
J Proteomics. 2021 May 15;239:104183. doi: 10.1016/j.jprot.2021.104183. Epub 2021 Mar 15.
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. SIGNIFICANCE: KD 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.
川崎病（KD）是一种全身性血管炎，可导致严重的心血管并发症，而特定生物标志物的开发和临床应用可能有助于诊断 KD 并避免某些并发症。为此，通过白细胞蛋白质组学和血清代谢组学检测，首次研究了伴有冠状动脉损伤（CAL）的急性 KD 患者的分子谱。与健康对照组相比，急性 KD 患者中共有 269 种差异丰富的蛋白质和 35 种差异丰富的代谢物，其丰度水平最高。其中，进一步分析了几种有前途的候选标志物蛋白和代谢物，如 ALPL、NAMPT 和 S100P 等表达上调的蛋白，以及 C1QB 和载脂蛋白家族成员等表达下调的蛋白。此外，还发现包括琥珀酸、dGMP、透明质酸、L-色氨酸、丙酰肉碱、肌苷和磷酸胆碱在内的代谢物在区分 KD 患者和健康对照组方面具有很高的准确性。有趣的是，急性 KD 患者中一组独特的蛋白质和代谢物的异常表达水平在静脉注射免疫球蛋白（IVIG）治疗后可恢复正常水平。总的来说，这项工作揭示了新的生物标志物和异常的氨基酸代谢是伴有 CAL 的 KD 患者的一个显著特征。意义：KD 常伴有危及生命的冠状动脉血管炎的发生。在这里，首次研究了伴有 CAL 的急性 KD 患者的白细胞蛋白质组学和血清代谢组学特征，在此鉴定的几个关键分子可作为 KD 诊断的辅助生物标志物。此外，代谢异常，尤其是氨基酸异常，在 KD 患者中尤为突出。有趣的是，急性 KD 患者中一组独特的蛋白质和代谢物的异常表达水平在 IVIG 治疗后可恢复正常水平。因此，这些发现可能有助于了解 IVIG 的作用以及 IVIG 耐药患者的潜在机制，从而为探索与 KD 相关的机制提供新的视角。
