丝氨酸、N-乙酰天冬氨酸可区分青少年特发性关节炎与健康对照：一项代谢组学横断面研究。

Serine, N-acetylaspartate differentiate adolescents with juvenile idiopathic arthritis compared with healthy controls: a metabolomics cross-sectional study.

机构信息

Department of Physiological Nursing, School of Nursing, University of California, San Francisco, 2 Koret Way, San Francisco, CA, 94131, USA.

School of Nursing, The University of Texas at Austin, 1710 Red River St, Austin, TX, 78712, USA.

出版信息

Pediatr Rheumatol Online J. 2022 Feb 10;20(1):12. doi: 10.1186/s12969-022-00672-z.

DOI:10.1186/s12969-022-00672-z

PMID:35144633

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8832851/

Abstract

BACKGROUND

In comparison with the general population, adolescents with juvenile idiopathic arthritis (JIA) are at higher risk for morbidity and mortality. However, limited evidence is available about this condition's underlying metabolic profile in adolescents with JIA relative to healthy controls. In this untargeted, cross-sectional metabolomics study, we explore the plasma metabolites in this population.

METHODS

A sample of 20 adolescents with JIA and 20 controls aged 13-17 years were recruited to complete surveys, provide medical histories and biospecimens, and undergo assessments. Fasting morning plasma samples were processed with liquid chromatography-mass spectrometry. Data were centered, scaled, and analyzed using generalized linear models accounting for age, sex, and medications (p-values adjusted for multiple comparisons using the Holm method). Spearman's correlations were used to evaluate relationships among metabolites, time since diagnosis, and disease severity.

RESULTS

Of 72 metabolites identified in the samples, 55 were common to both groups. After adjustments, 6 metabolites remained significantly different between groups. Alpha-glucose, alpha-ketoglutarate, serine, and N-acetylaspartate were significantly lower in the JIA group than in controls; glycine and cystine were higher. Seven additional metabolites were detected only in the JIA group; 10 additional metabolites were detected only in the control group. Metabolites were unrelated to disease severity or time since diagnosis.

CONCLUSIONS

The metabolic signature of adolescents with JIA relative to controls reflects a disruption in oxidative stress; neurological health; and amino acid, caffeine, and energy metabolism pathways. Serine and N-acetylaspartate were promising potential biomarkers, and their metabolic pathways are linked to both JIA and cardiovascular disease risk. The pathways may be a source of new diagnostic, treatment, or prevention options. This study's findings contribute new knowledge for systems biology and precision health approaches to JIA research. Further research is warranted to confirm these findings in a larger sample.

摘要

背景

相较于普通人群，青少年特发性关节炎（JIA）患者的发病率和死亡率更高。然而，目前关于 JIA 青少年患者相对于健康对照者的潜在代谢特征的证据有限。在这项非靶向、横断面代谢组学研究中，我们探索了该人群的血浆代谢物。

方法

我们招募了 20 名年龄在 13-17 岁的 JIA 青少年患者和 20 名对照者完成问卷调查、提供病史和生物样本，并接受评估。采集空腹清晨的血浆样本，用液相色谱-质谱法进行处理。使用广义线性模型对数据进行中心化、缩放和分析，模型考虑了年龄、性别和药物（使用 Holm 方法调整多重比较的 p 值）。使用 Spearman 相关性评估代谢物之间、从诊断到现在的时间以及疾病严重程度之间的关系。

结果

在样本中鉴定出的 72 种代谢物中，有 55 种在两组中都存在。调整后，有 6 种代谢物在两组间仍存在显著差异。JIA 组的 alpha-葡萄糖、alpha-酮戊二酸、丝氨酸和 N-乙酰天冬氨酸明显低于对照组；甘氨酸和胱氨酸则更高。仅在 JIA 组中检测到 7 种额外的代谢物；仅在对照组中检测到 10 种额外的代谢物。代谢物与疾病严重程度或从诊断到现在的时间无关。

结论

与对照组相比，JIA 青少年患者的代谢特征反映了氧化应激、神经健康以及氨基酸、咖啡因和能量代谢途径的紊乱。丝氨酸和 N-乙酰天冬氨酸是很有前途的潜在生物标志物，其代谢途径与 JIA 和心血管疾病风险都有关。这些途径可能为新的诊断、治疗或预防方法提供来源。本研究的发现为 JIA 研究的系统生物学和精准健康方法提供了新的知识。有必要在更大的样本中进一步验证这些发现。