Data from: Serum metabolomics predicts treatment response in myasthenia gravis

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.