Metabolomics analysis identifies a lipidomic profile in treatment-naïve juvenile dermatomyositis patients vs healthy control subjects. (29th June 2021)

• Record Type: Journal Article
• Authors: Dvergsten, Jeffrey A; Reed, Ann M; Landerman, Lawrence; Pisetsky, David S; Ilkayeva, Olga; Huffman, Kim M
• Is Part Of: Rheumatology. Volume 61:Number 4(2022)
• Page Start: 1699
• Page End: 1708
• Publication Date: 2021-06-29
• Subjects: JDM -- metabolomics -- biomarkers -- principal components analysis -- fatty acid oxidation -- acylcarnitines -- ceramide -- insulin resistance; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keab520
• Languages: English
• ISSNs: 1462-0324

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.