Department of Pediatrics, Duke Children's Hospital, Duke University Medical Center.
Department of Medicine and Immunology, Duke University Medical Center and Research Service, Durham VA Medical Center.
Rheumatology (Oxford). 2022 Apr 11;61(4):1699-1708. doi: 10.1093/rheumatology/keab520.
To perform an exploratory study to identify a JDM serum metabolic profile that differs from healthy controls (HCs) and responds to immunosuppressive treatment.
Blood was collected from 9 HCs and 10 patients diagnosed with probable (n = 4) or definite (n = 6) JDM based on the criteria of Bohan and Peter for myositis, with 7 of the 10 providing longitudinal samples following initiation of treatment; these patients comprised the treatment-naïve cohort. Sera underwent mass spectroscopy-based measurements of targeted metabolic intermediates, including 15 amino acids, 45 acylcarnitines (ACs), 15 ceramides and 29 sphingomyelins. Principal components analysis reduced metabolites into smaller sets of factors each comprised of correlated metabolic intermediates. Factor scores and metabolite concentrations were compared with HCs using two-sample t-tests while treatment effects were evaluated using paired t-tests.
Of eight principal components analysis-derived metabolite factors (one AC, two amino acids, three sphingosine and two ceramide), two were significantly associated with JDM: one AC factor containing mostly long-chain ACs (P = 0.049) and one ceramide factor (P < 0.01). For 12 individual ACs, mostly long chain, and three ceramides, concentrations were significantly greater for JDM than HCs. Factors based on these individual metabolites showed decreasing scores with treatment (P = 0.03 and P < 0.01, respectively).
While additional validation is needed, these lipids have potential as JDM serum diagnostic and/or treatment biomarkers. Additionally, the significant association of long-chain ACs and ceramides with JDM offers insights regarding pathogenesis, implicating dysregulation of mitochondrial fatty acid β-oxidation.
开展一项探索性研究，以确定与健康对照（HCs）不同且对免疫抑制治疗有反应的 JDM 血清代谢谱。
采集了 9 名 HCs 和 10 名根据 Bohan 和 Peter 制定的肌炎标准诊断为可能（n = 4）或明确（n = 6）的 JDM 患者的血液，其中 10 名患者中有 7 名在开始治疗后提供了纵向样本；这些患者构成了治疗初治队列。对血清进行了基于质谱的靶向代谢中间产物测量，包括 15 种氨基酸、45 种酰基肉碱（ACs）、15 种神经酰胺和 29 种鞘磷脂。主成分分析将代谢物减少为更小的因子集，每个因子都包含相关的代谢中间产物。使用两样本 t 检验比较因子得分和代谢物浓度与 HCs，使用配对 t 检验评估治疗效果。
在八个主成分分析衍生的代谢物因子（一个 AC、两个氨基酸、三个神经鞘氨醇和两个神经酰胺）中，有两个与 JDM 显著相关：一个主要包含长链 AC 的 AC 因子（P = 0.049）和一个神经酰胺因子（P < 0.01）。对于 12 种长链 AC 和三种神经酰胺，JDM 中的浓度明显高于 HCs。基于这些单个代谢物的因子显示出随着治疗的减少（P = 0.03 和 P < 0.01）。
尽管需要进一步验证，但这些脂质有可能成为 JDM 血清诊断和/或治疗生物标志物。此外，长链 ACs 和神经酰胺与 JDM 的显著关联为发病机制提供了深入的了解，表明线粒体脂肪酸β氧化的失调。
