Abstract：
OBJECTIVE: Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease characterized by sterile bone inflammation; however, its pathophysiology is poorly understood. Thus, this study aimed to characterize the serum proteomic profiles of patients with CRMO to better understand the molecular mechanisms underpinning CRMO pathogenesis.
METHODS: Proteomic profiling of the sera collected from 11 patients with CRMO (five patients were in active phase, six were in inactive phase) was conducted using liquid chromatography-mass spectrometry. Sera from four children without inflammatory diseases were used as controls. Pathway analysis was performed to identify the upregulated and downregulated proteins in patients with active CRMO.
RESULTS: Compared with the control group, 19 and 41 proteins were upregulated and downregulated, respectively, in patients with active CRMO. Pathway and process enrichment analyses revealed that axon guidance was the most enriched category of upregulated proteins in patients with active CRMO, followed by neutrophil degranulation and mitogen-activated protein kinase cascade regulation. In comparison to patients with inactive CRMO, 36 proteins, including 11 keratin proteins, were upregulated and highly enriched in the intermediate filament organization category. Rho GTPase pathway-related proteins were downregulated in ibuprofen-treated patients.
CONCLUSIONS: Proteomic analysis identified upregulated proteins in the sera of patients with acute CRMO. These proteins can be used as biomarkers for disease diagnosis and activity. Furthermore, we anticipate that this study will contribute to a deeper understanding of the pathophysiology of CRMO, which, in turn, will contribute to the discovery of potential novel therapeutic targets.
METHODS: Proteomic profiling of the sera collected from 11 patients with CRMO (five patients were in active phase, six were in inactive phase) was conducted using liquid chromatography-mass spectrometry. Sera from four children without inflammatory diseases were used as controls. Pathway analysis was performed to identify the upregulated and downregulated proteins in patients with active CRMO.
RESULTS: Compared with the control group, 19 and 41 proteins were upregulated and downregulated, respectively, in patients with active CRMO. Pathway and process enrichment analyses revealed that axon guidance was the most enriched category of upregulated proteins in patients with active CRMO, followed by neutrophil degranulation and mitogen-activated protein kinase cascade regulation. In comparison to patients with inactive CRMO, 36 proteins, including 11 keratin proteins, were upregulated and highly enriched in the intermediate filament organization category. Rho GTPase pathway-related proteins were downregulated in ibuprofen-treated patients.
CONCLUSIONS: Proteomic analysis identified upregulated proteins in the sera of patients with acute CRMO. These proteins can be used as biomarkers for disease diagnosis and activity. Furthermore, we anticipate that this study will contribute to a deeper understanding of the pathophysiology of CRMO, which, in turn, will contribute to the discovery of potential novel therapeutic targets.
摘要：
目的：慢性复发性多灶性骨髓炎（CRMO）是一种以无菌骨炎症为特征的自身炎症性疾病；然而，对其病理生理学了解甚少。因此，本研究旨在表征CRMO患者的血清蛋白质组学特征，以更好地了解支撑CRMO发病机制的分子机制。
方法：从11名CRMO患者收集的血清的蛋白质组学分析（5名患者处于活跃期，六个处于非活性相）使用液相色谱-质谱法进行。来自四个没有炎症性疾病的儿童的血清被用作对照。进行通路分析以鉴定患有活动性CRMO的患者中上调和下调的蛋白质。
结果：与对照组相比，19和41种蛋白质上调和下调，分别,活跃的CRMO患者。途径和过程富集分析显示，轴突导向是CRMO活跃患者中上调蛋白含量最高的一类。其次是中性粒细胞脱颗粒和丝裂原活化蛋白激酶级联调节。与CRMO不活跃的患者相比，36种蛋白质,包括11种角蛋白，在中间长丝组织类别中被上调和高度富集。布洛芬治疗患者RhoGTP酶途径相关蛋白下调。
结论：蛋白质组学分析发现急性CRMO患者血清中的蛋白质上调。这些蛋白质可用作疾病诊断和活性的生物标志物。此外，我们预计这项研究将有助于更深入地了解CRMO的病理生理学，which,反过来,将有助于发现潜在的新治疗靶点。
方法：从11名CRMO患者收集的血清的蛋白质组学分析（5名患者处于活跃期，六个处于非活性相）使用液相色谱-质谱法进行。来自四个没有炎症性疾病的儿童的血清被用作对照。进行通路分析以鉴定患有活动性CRMO的患者中上调和下调的蛋白质。
结果：与对照组相比，19和41种蛋白质上调和下调，分别,活跃的CRMO患者。途径和过程富集分析显示，轴突导向是CRMO活跃患者中上调蛋白含量最高的一类。其次是中性粒细胞脱颗粒和丝裂原活化蛋白激酶级联调节。与CRMO不活跃的患者相比，36种蛋白质,包括11种角蛋白，在中间长丝组织类别中被上调和高度富集。布洛芬治疗患者RhoGTP酶途径相关蛋白下调。
结论：蛋白质组学分析发现急性CRMO患者血清中的蛋白质上调。这些蛋白质可用作疾病诊断和活性的生物标志物。此外，我们预计这项研究将有助于更深入地了解CRMO的病理生理学，which,反过来,将有助于发现潜在的新治疗靶点。
