Abstract
BackgroundPolymyositis (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.MethodsLipidomic 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.ResultsThe 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.ConclusionsSerum 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.
Highlights
Polymyositis (PM) and dermatomyositis (DM) are severe chronic autoimmune diseases, characterized by muscle fatigue and low muscle endurance
fatty acids (FA) composition of serum total lipids in patients with PM/ DM and healthy individuals (HI) First, as a screening test we examined the FA composition of total serum lipids in patients with PM/DM and HI using gas-chromatography flame ionization detector (GC-FID)
The FA profiles were altered in patients with PM/DM compared to HI (Table 1)
Summary
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; 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. Polymyositis (PM) and dermatomyositis (DM) are chronic autoimmune disorders characterized by skeletal muscle weakness, fatigue and damage. Conventional treatment of PM and DM is based on immunosuppression including high doses of glucocorticoids (GC) often in combination with other immunosuppressive drugs [1, 2], but despite clinical improvement, only a few patients fully restore previous muscle strength. Changes in muscle lipid metabolism may be caused by ER stress, chronic inflammation or immunosuppressive treatment as suggested by recent reports [9, 10] and in turn lead to altered lipid profiles contributing to persistent muscle impairment. Deviations in the phospholipid levels or FA composition are associated with impaired muscle performance while dietary supplementation with unsaturated FA improves skeletal muscle mass and strength [14,15,16,17,18]
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