Proteomic analysis of Crow-Fukase syndrome

目标：本研究的目的是建立一种诊断方法，通过全面和快速地鉴定患者血清中的肽片段，在随后的病理阶段中检测哪些分子已经降解，以及接下来会发生什么，从而开发一种诊断方法，有助于确定评估病理状况、营养支持和药物治疗策略的适当方向。方法：Protosera Inc.开发的新蛋白质组分析技术，应用于来自正常受试者和患有Crow-dichroase综合征（POEMS综合征）（一种顽固性炎性病症）的同一患者的处于稳定（在诊断时）、恶化、DIC和MOF阶段的未处理血清样品的差异谱分析，并且对显著不同的MS峰进行MS/MS从头测序。对来自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品进行了类似的分析。结果：我们鉴定了94个低分子量肽片段，其特征性地出现在DIC和MOF阶段。这些肽片段来源于载体蛋白，如甲状腺素运载蛋白和蛋白酶抑制剂，如α1-抗胰蛋白酶。此外，这94个肽片段中的一些与在相应的早期癌症患者中特征性地观察到的肽片段峰一致。讨论内容：出现在血液中的低分子量肽片段的模式反映了表征生物环境的蛋白酶的活化，包括正常受试者和癌症、DIC或MOF患者的蛋白酶的活化，从而提供关于病理状况的有价值的信息。我们认为，这些结果将导致一种方法的发展，有助于确定适当的方向的战略，病理诊断，营养支持和药物治疗。

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.