Proteomics based markers of clinical pain severity in juvenile idiopathic arthritis.
Proteomics based markers of clinical pain severity in juvenile idiopathic arthritis.
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基于蛋白质组学的基于少年特发性关节炎的临床疼痛严重程度的标志物。
DOI：
10.1186/s12969-022-00662-1
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发表时间：
2022-01-15
期刊：
影响因子：
--
通讯作者：
Upadhyay J
中科院分区：
文献类型：
--
作者：
Van Der Heijden H;Fatou B;Sibai D;Hoyt K;Taylor M;Cheung K;Lemme J;Cay M;Goodlett B;Lo J;Hazen MM;Halyabar O;Meidan E;Schreiber R;Jaimes C;Ecklund K;Henderson LA;Chang MH;Nigrovic PA;Sundel RP;Steen H;Upadhyay J
幼年特发性关节炎（JIA）是一组发生在16岁或以下儿童中的自身免疫性风湿性疾病。虽然众所周知，炎症和非炎症状态下可能会经历疼痛，但关于可能导致JIA疼痛的分子机制仍不清楚。因此，在这项初步研究中，我们探讨了血清蛋白质组的变异性与疼痛的严重程度在一个队列的JIA患者。使用液相色谱/质谱法（LC/MS）评估了15名JIA患者（男性和女性，12.7 ± 2.8岁）的血清样本。进行相关性分析，以确定蛋白质水平和自我报告的临床疼痛严重程度之间的关系。此外，还评估了疼痛相关蛋白的表达如何与炎症标志物（红细胞沉降率（ESR））或中枢神经系统的形态学特性（皮质下体积和皮质厚度）相关。在JIA组群中鉴定了306种蛋白质，其中14种与临床疼痛严重程度显著相关（p < 0.05）。所鉴定的疼痛相关蛋白的功能特性包括但不限于体液免疫（IGLV3.9）、炎症反应（PRG 4）和血管生成（ANG）。此外，还观察了疼痛相关蛋白与ESR（IGHV 3.9、PRG 4、CST 3、VWF、ALB）以及尾状核体积（BTD、AGT、IGHV 3.74）和岛叶皮质厚度（BTD、LGALS 3BP）之间的相关性。目前的蛋白质组学研究结果表明，炎症和非炎症介导的机制与JIA疼痛的潜在因素。使用更大的患者队列和纵向研究设计验证这些初步观察结果可能进一步指向JIA疼痛的新血清学标志物。在线版本包含补充材料，可通过10.1186/s12969-022-00662-1获得。在目前的初步研究中，确定了JIA患者与疼痛严重程度相关的血清蛋白。疼痛相关蛋白主要在免疫或炎症过程中发挥功能作用。同时观察到疼痛相关蛋白与ESR和CNS形态学改变的相关性。需要更大规模的纵向研究来确定蛋白质组的评估是否可以为JIA中识别新的镇痛靶点提供平台。在线版本包含补充材料，可通过10.1186/s12969-022-00662-1获得。
Juvenile idiopathic arthritis (JIA) is a cluster of autoimmune rheumatic diseases occurring in children 16 years of age or less. While it is well-known that pain may be experienced during inflammatory and non-inflammatory states, much remains ambiguous regarding the molecular mechanisms that may drive JIA pain. Thus, in this pilot study, we explored the variability of the serum proteomes in relation to pain severity in a cohort of JIA patients. Serum samples from 15 JIA patients (male and female, 12.7 ± 2.8 years of age) were assessed using liquid chromatography/mass spectrometry (LC/MS). Correlation analyses were performed to determine the relationships among protein levels and self-reported clinical pain severity. Additionally, how the expression of pain-associated proteins related to markers of inflammation (Erythrocyte Sedimentation Rate (ESR)) or morphological properties of the central nervous system (subcortical volume and cortical thickness) implicated in JIA were also evaluated. 306 proteins were identified in the JIA cohort of which 14 were significantly (p < 0.05) associated with clinical pain severity. Functional properties of the identified pain-associated proteins included but were not limited to humoral immunity (IGLV3.9), inflammatory response (PRG4) and angiogenesis (ANG). Associations among pain-associated proteins and ESR (IGHV3.9, PRG4, CST3, VWF, ALB), as well as caudate nucleus volume (BTD, AGT, IGHV3.74) and insular cortex thickness (BTD, LGALS3BP) were also observed. The current proteomic findings suggest both inflammatory- and non-inflammatory mediated mechanisms as potential factors associated with JIA pain. Validation of these preliminary observations using larger patient cohorts and a longitudinal study design may further point to novel serologic markers of pain in JIA. The online version contains supplementary material available at 10.1186/s12969-022-00662-1. In the current preliminary study, serum proteins associated with pain severity were identified in JIA patients. Pain-associated proteins had functional roles predominantly in immune or inflammatory processes. Correlations of pain-associated proteins with ESR and altered CNS morphology were also observed with ESR and altered CNS morphology were also observed. Larger-scale as well as longitudinal studies are needed to determine if evaluation of the proteome may provide a platform for identifying novel analgesic targets in JIA. The online version contains supplementary material available at 10.1186/s12969-022-00662-1.
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