Metabolomics Analysis Identifies a Lipidomic Profile in Treatment Naïve Juvenile Dermatomyositis Patients versus Healthy Control Subjects.

OBJECTIVES To perform an exploratory study to identify a juvenile dermatomyositis (JDM) serum metabolic profile that differs from healthy controls (HC) and responds to immunosuppressive treatment. METHODS Blood was collected from nine HC and 10 patients diagnosed with probable (n = 4) or definite (n = 6) JDM based on the criteria of Bohan and Peter for myositis with seven of these 10 providing longitudinal samples following initiation of treatment; these patients comprised the treatment naive (TN) cohort. Sera underwent mass-spectroscopy-based measurements of targeted metabolic intermediates including 15 amino acids (AAs), 45 acylcarnitines (ACs), 15 ceramides, and 29 sphingomyelins. Principal components analysis (PCA) reduced metabolites into smaller sets of factors each comprised of correlated metabolic intermediates. Factor scores and metabolite concentrations were compared with HC using two-sample t-tests while treatment effects were evaluated using paired t-tests. RESULTS Of eight PCA-derived metabolite factors (1 AC, 2 AA, 3 sphingosine, and 2 ceramide), two were significantly associated with juvenile DM: one AC factor containing mostly long chain ACs (LCAC, 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 juvenile DM than HC. Factors based on these individual metabolites showed declining 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.