Affiliation:
1. Department of Pediatrics, Duke Children’s Hospital, Duke University Medical Center
2. Department of Medicine and Immunology, Duke University Medical Center and Research Service, Durham VA Medical Center
3. Department of Medicine, Duke Molecular Physiology Institute, Duke School of Medicine, Durham, NC, USA
Abstract
Abstract
Objectives
To perform an exploratory study to identify a JDM serum metabolic profile that differs from healthy controls (HCs) and responds to immunosuppressive treatment.
Methods
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.
Results
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).
Conclusion
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.
Publisher
Oxford University Press (OUP)
Subject
Pharmacology (medical),Rheumatology
Cited by
5 articles.
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