Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration.
Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration.
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DOI：
10.1038/s41598-020-72654-8
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发表时间：
2020-09-24
影响因子：
4.6
通讯作者：
Casaccia P
中科院分区：
文献类型：
--
作者：
Amatruda M;Petracca M;Wentling M;Inbar B;Castro K;Chen EY;Kiebish MA;Edwards K;Inglese M;Casaccia P
确诊为原发性进行性多发性硬化症(PPMS)的患者的病程尚不确定。为了确定参与疾病演变的潜在信号通路，我们对非疾病对照组(n = 8)和原发进展性多发性硬化症(PPMS，n = 19)患者以及快速(PPMS-P，n = 9)或慢(PPMS-NP，n = 10)病程的患者的血浆进行了探索性的无偏脂组分析，基于一年评估中新T2病变的残疾恶化和/或磁共振可见表现。偏最小二乘-MS/MSALL脂体组数据集的判别分析，确定了驱动组聚类的脂类。与对照组相比，PPMS患者血浆中神经鞘磷脂-D18：1/14：0和单己糖神经酰胺-D18：1/20：0的含量差异显著，其水平与疾病进展的MRI征象相关。溶血磷脂酸-18：2(LPA-18：2)是PPMS患者中唯一丰度显著降低的脂类，其水平与神经功能缺失程度呈负相关。LPA-18：2水平在疾病进展较快的患者中检测到降低，无论采用何种治疗，这些发现在独立的继发性进展性(SPMS)患者队列中得到验证，但在第三组复发-缓解(RRMS)患者中未得到验证。总之，我们的分析表明，鞘磷脂-D18：1/14：0、单己糖神经酰胺-D18：1/20：0和LPA-18：2可能是未来研究的重要靶点，旨在了解MS的疾病进展。
The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.
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影响因子：
5.7
作者：
Reuter, Martin;Schmansky, Nicholas J.;Rosas, H. Diana;Fischl, Bruce
通讯作者：
Fischl, Bruce
影响因子：
7.1
作者：
Schmitz K;Brunkhorst R;de Bruin N;Mayer CA;Häussler A;Ferreiros N;Schiffmann S;Parnham MJ;Tunaru S;Chun J;Offermanns S;Foerch C;Scholich K;Vogt J;Wicker S;Lötsch J;Geisslinger G;Tegeder I
通讯作者：
Tegeder I
影响因子：
3.3
作者：
Del Boccio, Piero;Pieragostino, Damiana;Urbani, Andrea
通讯作者：
Urbani, Andrea
影响因子：
3.7
作者：
Prüss H;Rosche B;Sullivan AB;Brommer B;Wengert O;Gronert K;Schwab JM
通讯作者：
Schwab JM
影响因子：
4.6
作者：
Nogueras, L.;Gonzalo, H.;Brieva, L.
通讯作者：
Brieva, L.