NMR-based serum and muscle metabolomics for diagnosis and activity assessment in idiopathic inflammatory myopathies.

Objectives: Differentiating smoldering disease activity from weakness due to fatty replacement of atrophied muscle can often be a challenge in the idiopathic inflammatory myositis (IIM). We aimed to identify the metabolic disturbances associated with IIM and if these changes can aid in the assessment of disease activity.

Methods: Metabolic profiles of sera (N = 99) and muscle (N = 21) from patients with IIM (ACR-EULAR criteria) were compared with healthy control (HC) samples (N = 75 for serum and N = 12 for muscle tissues) employing 800 MHz NMR (Nuclear Magnetic Resonance) spectroscopy. Metabolic disparity between IIM and HC was established based on Partial Least Squares Discriminant Analysis (PLS-DA) and the discriminatory metabolites were identified based on variable importance in projection (VIP) statistics (-value < .05, corrected for false discovery rate (FDR)).

Results: Serum metabolomics profiles were distinctive in IIM as compared to HC, with a visible shift to anaerobic metabolism (increased lactate, low glucose), oxidative defect (high Phenylalanine/tyrosine), decreased muscle mass (low serum creatinine), increased muscle catabolism (increased branched-chain amino acids), and dyslipidemia (higher lipids, higher very low-density lipoprotein [VLDL]/low-density lipoprotein [LDL] ratio, lower polyunsaturated fatty acid [PUFA]). The sera of active IIM patients were characterized by anaerobic metabolism (low glucose), loss of muscle mass (low creatinine, amino acids), and oxidative defect (high Phenylalanine/tyrosine). Three metabolites (isopropanol, succinate, and glycine) were distinctive in muscle tissue metabolomics. NMR-based serum metabolic disparity was lacking between different clinical subsets of IIM.

Conclusion: Serum and muscle tissue metabolomics have the potential to distinguish (a) IIM from HC and (b) active IIM from inactive IIM irrespective of disease subtype.