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血清氨基酸谱分析在多发性硬化症临床结局鉴别中的应用。

Serum amino acid profiling in differentiating clinical outcomes of multiple sclerosis.

机构信息

Department of Neurology, 10th Military Research Hospital and Polyclinic, Bydgoszcz, Poland.

Sanitas - Neurology Outpatient Clinic, Bydgoszcz, Poland.

出版信息

Neurol Neurochir Pol. 2023;57(5):414-422. doi: 10.5603/PJNNS.a2023.0054. Epub 2023 Aug 1.

Abstract

AIM OF THE STUDY

Amino acid metabolism is crucial for regulating immune responses and can be monitored in blood serum samples. This study aimed to analyse serum amino acid profiles in people with multiple sclerosis (pwMS), taking into account differences depending on the disease outcomes.

CLINICAL RATIONALE FOR THE STUDY

Serum amino acid profiling is a promising, reproducible and minimally invasive technology, available at different stages of the disease, enabling the search for a specific biomarker to differentiate MS clinical outcomes.

MATERIAL AND METHODS

The serum concentrations of 29 amino acids were determined using high-performance liquid chromatography mass spectrometry.

RESULTS

A total of 121 pwMS (41 relapsing-remitting MS-RRMS; 55 secondary progressive MS - SPMS; and 25 primary progressive MS-RRMS) with a median Expanded Disability Status Scale (EDSS) score of 6 and 53 healthy controls (HCs) were included. We found significantly higher serum total amino acids concentrations in pwMS compared to HCs. Serum concentrations of arginine, 1-methyl-L-histidine and proline were higher in pwMS, while circulating citrulline, α-aminobutyric acid and tryptophan were lower in pwMS. We observed significant differences in serum total amino acids concentrations depending on MS type, with the highest level in the PPMS group and the lowest in the RRMS group. We found significantly higher serum levels of beta-aminoisobutyric acid in PPMS patients compared to those with RRMS and SPMS, and significantly higher serum levels of aspartic acid in PPMS patients compared to RRMS patients. From visual inspection, no trend was observed in total amino acids concentration with respect to the EDSS score. When analysing serum total amino acids concentration in pwMS with EDSS ≤ 5 compared to those with EDSS > 5, no significant differences were found.

CONCLUSIONS AND CLINICAL IMPLICATIONS

Amino acid metabolism is altered in pwMS and depends on the clinical type of the disease. Further studies are needed to determine whether serum metabolomic profiling of amino acids may have an application in the search for clinical phenotype-specific MS biomarkers.

摘要

研究目的

氨基酸代谢对于调节免疫反应至关重要,可以通过血清样本进行监测。本研究旨在分析多发性硬化症(pwMS)患者的血清氨基酸谱,同时考虑到不同疾病结局的差异。

研究的临床意义

血清氨基酸谱分析是一种有前途、可重复且微创的技术,可在疾病的不同阶段使用,从而能够寻找特定的生物标志物来区分 MS 的临床结局。

材料和方法

采用高效液相色谱-质谱法测定 29 种氨基酸的血清浓度。

结果

共纳入 121 名 pwMS(41 名复发缓解型 MS-RRMS;55 名继发进展型 MS-SPMS;25 名原发进展型 MS-RRMS),中位扩展残疾状况量表(EDSS)评分为 6 分,以及 53 名健康对照者(HCs)。我们发现 pwMS 的血清总氨基酸浓度明显高于 HCs。pwMS 组血清精氨酸、1-甲基-L-组氨酸和脯氨酸浓度升高,而血清瓜氨酸、α-氨基丁酸和色氨酸浓度降低。我们观察到 MS 类型之间血清总氨基酸浓度存在显著差异,PPMS 组最高,RRMS 组最低。我们发现 PPMS 患者的血清β-氨基异丁酸水平明显高于 RRMS 和 SPMS 患者,PPMS 患者的血清天门冬氨酸水平明显高于 RRMS 患者。从直观上看,EDSS 评分与总氨基酸浓度之间没有趋势。当分析 EDSS≤5 的 pwMS 患者与 EDSS>5 的 pwMS 患者的血清总氨基酸浓度时,未发现显著差异。

结论和临床意义

pwMS 患者的氨基酸代谢发生改变,且与疾病的临床类型有关。需要进一步的研究来确定血清氨基酸代谢组学分析是否可用于寻找针对 MS 临床表型特异性的生物标志物。

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