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. 2018 May 2;20(1):83.
doi: 10.1186/s13075-018-1579-y.

Targeted lipidomics analysis identified altered serum lipid profiles in patients with polymyositis and dermatomyositis

Joan Raouf  1 , Helena Idborg  1 , Petter Englund  2 , Helene Alexanderson  1 , Maryam Dastmalchi  1 , Per-Johan Jakobsson  1 , Ingrid E Lundberg  1 , Marina Korotkova  3
Affiliations

Targeted lipidomics analysis identified altered serum lipid profiles in patients with polymyositis and dermatomyositis

Joan Raouf et al. Arthritis Res Ther. .

Abstract

Background: Polymyositis (PM) and dermatomyositis (DM) are severe chronic autoimmune diseases, characterized by muscle fatigue and low muscle endurance. Conventional treatment includes high doses of glucocorticoids and immunosuppressive drugs; however, few patients recover full muscle function. One explanation of the persistent muscle weakness could be altered lipid metabolism in PM/DM muscle tissue as we previously reported. Using a targeted lipidomic approach we aimed to characterize serum lipid profiles in patients with PM/DM compared to healthy individuals (HI) in a cross-sectional study. Also, in the longitudinal study we compared serum lipid profiles in patients newly diagnosed with PM/DM before and after immunosuppressive treatment.

Methods: Lipidomic profiles were analyzed in serum samples from 13 patients with PM/DM, 12 HI and 8 patients newly diagnosed with PM/DM before and after conventional immunosuppressive treatment using liquid chromatography tandem mass spectrometry (LC-MS/MS) and a gas-chromatography flame ionization detector (GC-FID). Functional Index (FI), as a test of muscle performance and serum levels of creatine kinase (s-CK) as a proxy for disease activity were analyzed.

Results: The fatty acid (FA) composition of total serum lipids was altered in patients with PM/DM compared to HI; the levels of palmitic (16:0) acid were significantly higher while the levels of arachidonic (20:4, n-6) acid were significantly lower in patients with PM/DM. The profiles of serum phosphatidylcholine and triacylglycerol species were changed in patients with PM/DM compared to HI, suggesting disproportionate levels of saturated and polyunsaturated FAs that might have negative effects on muscle performance. After immunosuppressive treatment the total serum lipid levels of eicosadienoic (20:2, n-6) and eicosapentaenoic (20:5, n-3) acids were increased and serum phospholipid profiles were altered in patients with PM/DM. The correlation between FI or s-CK and levels of several lipid species indicate the important role of lipid changes in muscle performance and inflammation.

Conclusions: Serum lipids profiles are significantly altered in patients with PM/DM compared to HI. Moreover, immunosuppressive treatment in patients newly diagnosed with PM/DM significantly affected serum lipid profiles. These findings provide new evidence of the dysregulated lipid metabolism in patients with PM/DM that could possibly contribute to low muscle performance.

Keywords: Dermatomyositis; Fatty acids; Immunosuppressive treatment; Lipidomics; Phospholipids; Polymyositis.

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Conflict of interest statement

Ethics approval and consent to participate

The regional ethics committee in Stockholm granted the approval (N2005/792–31/4) and all participants gave informed consent to participate in the study.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a Serum lipid species in patients with polymyositis or dermatomyositis compared to healthy individuals. PC, phosphatidylcholine; TG, triacylglycerol. Results are expressed as percentage area (area %) (mean ± SE): *p < 0.05, **p < 0.01, for patients with polymyositis (PM)/dermatomyositis (DM) versus healthy individuals. b, c Score plots from unsupervised clustering by principal component analysis (PCA) (b) and supervised clustering by orthogonal projection to latent structures (OPLS) (c) are shown. Healthy individuals are represented by blue squares and patients with PM/DM by red triangles. d The corresponding loading plot obtained from OPLS analysis. Lipids important for the separation of patients with PM/DM from controls are highlighted in red
Fig. 2
Fig. 2
Serum lipid species in patients with polymyositis or dermatomyositis before and after immunosuppressive treatment. PC, phosphatidylcholine; PE, phosphatidylethanolamine; LPC, lysophosphatidylcholine; TG, triacylglycerol. Results are expressed as percentage area (Area %) (mean ± SE): *p < 0.05 for after treatment versus before treatment
Fig. 3
Fig. 3
Results of multivariate analysis of the lipid species data obtained from patients with polymyositis (PM)/dermatomyositis (DM) before and after immunosuppressive treatment. a Score plot from unsupervised clustering by principal component analysis (PCA). Samples from patients with PM/DM before treatment are shown as blue squares and after treatment as red triangles. b Score plot visualizing separation of the samples from patients before and after treatment based on supervised clustering (OPLS). Paired before-treatment and after-treatment samples are shown in the same color. c The corresponding loading plot obtained from OPLS. Lipids important for the separation of patients before and after treatment are highlighted in red
Fig. 4
Fig. 4
a Serum creatine kinase levels and b functional index (FI) in patients with polymyositis or dermatomyositis before and after immunosuppressive treatment. Results are expressed as μcat/L and percentage, respectively (mean ± SE)
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