Data from: Serum metabolomics predicts treatment response in myasthenia gravis
Data files
Jul 02, 2023 version files 234.16 KB
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README.md
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Supp._Table1._Tandem_MS_Validated_Metabolites.xlsx
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Supp._Table2._Test_Statistics_For_Targeted_and_Validated_Untargeted_Metabolites.xlsx
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Supp._Table3._Thymectomy___prednisone_6_months_vs_baseline.xlsx
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Supp._Table4._Pathway_analysis_Mummichog.xlsx
Abstract
High-dose prednisone is the primary initial therapy for myasthenia gravis (MG) but upwards of a third of patients do not respond to treatment. No biomarkers can predict clinical responsiveness to corticosteroid treatment. We conducted a discovery-based study to identify treatment responsive biomarkers in MG using sera obtained at study entry to the thymectomy clinical trial (MGTX), an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone. We applied ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry to obtain comparative serum metabolomic and lipidomic profiles at study entry to correlate with treatment response at 6 months. Treatment response was assessed using validated outcome measures of minimal manifestation status (MMS), MG-Activities of Daily Living (MG-ADL), Quantitative MG (QMG) score, or a strictly defined composite measure of response. Increased levels of phospholipids were associated with treatment response as assessed by QMG, MMS, and the Responders classification, but all measures showed limited overlap in metabolomic profiles, in particular the MG-ADL. A panel including histidine, free fatty acid (13:0), γ-cholestenol and guanosine was highly predictive of the strictly defined treatment response measure. The AUC in Responders' prediction for these markers was 0.90. Pathway analysis suggests that xenobiotic metabolism could play a major role in treatment resistance. We have defined a metabolomic and lipidomic profile that can now undergo validation as treatment predictive markers for MG patients undergoing corticosteroid therapy. Distinct metabolomic profiles were appreciated for each outcome measure.
Methods
Serum samples from clinical trial. See manuscript for details.