Proteomic analysis of Crow-Fukase syndrome

目的：本研究旨在建立一种诊断方法，通过在随后的病理阶段全面、快速地识别患者血清中的多肽片段，从而建立一种检测哪些分子已经降解以及下一步将发生什么进展的诊断方法，从而开发一种有助于确定评估病理状况、营养支持和药物治疗的策略的适当方向的诊断方法。方法：应用Protosera公司开发的新的蛋白质组分析技术，对正常人和同一顽固性炎症性疾病Crow-Fukase综合征(POEMS综合征)患者在稳定期(诊断时)、加重期、DIC期和MOF期的血清样本进行差异分析，并对显著不同的MS峰进行MS/MS从头测序。对正常受试者和患有六种不同类型早期癌症的患者的未经处理的血清样本进行了类似的分析。结果：我们鉴定出94个低分子多肽片段，它们典型地出现在DIC和MOF阶段。这些多肽片段来自载体蛋白，如转甲状腺素和蛋白酶抑制剂，如α1-抗胰蛋白酶。此外，这94个多肽片段中的一些与在各自早期癌症患者中典型观察到的多肽片段峰一致。讨论：血液中出现的低分子多肽片段的模式反映了表征生物环境的蛋白酶的激活，包括正常受试者和癌症、DIC或MOF患者的生物环境，从而提供了关于病理条件的有价值的信息。我们认为，这些结果将导致一种方法的发展，该方法有助于确定病理条件诊断、营养支持和药物治疗的适当方向。

Objective : This study aimed to establish a diagnostic method for detecting what molecules have been degraded and what is going to progress next, by comprehensively and rapidly identifying peptide fragments in the patient's serum throughout subsequent pathological stages, thereby developing a diagnostic method that contributes to determining the appropriate direction of strategies for assessment of the pathological condition, nutritional support, and drug treatment. Methods : New proteome analysis technology, developed by Protosera Inc., was applied for the differential profiling of untreated serum samples from normal subjects and the same patient with Crow-Fukase Syndrome (POEMS Syndrome),an intractable inflammatory disorder, in the stable (at the time of diagnosis),exacerbation, DIC, and MOF stages, and MS/MS de novo sequencing of significantly different MS peaks was performed. A similar analysis was conducted of untreated serum samples from normal subjects and patients with six different types of early cancer. Results : We identified 94 low-molecular-weight peptide fragments that characteristically appeared in the DIC and MOF stages. These peptide fragments were derived from carrier proteins, such as transthyretin and protease inhibitors such as α1-antitrypsin. Moreover, some of these 94 peptide fragments coincided with the peptide fragment peaks that were characteristically observed in the respective early cancer patients. Discussion : The patterns of low-molecular-weight peptide fragments that appear in the blood reflect the activation of proteases characterizing the biological environment, including that of normal subjects and patients with cancer, DIC, or MOF, thereby providing valuable information on pathological conditions. We consider that these results will lead to the development of a method that contributes to determining the appropriate direction of strategies for pathological condition diagnosis, nutritional support, and drug treatment.