title: Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis.
abstract: To determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire (1)H-NMR and ultra high pressure liquid chromatography (UPLC)-MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that (1)H-NMR and UPLC-MS/MS may be promising tools for predicting response to rituximab.
authors.affiliation: Department of Nutritional Sciences , Dell Pediatric Research Institute, University of Texas at Austin , Austin, Texas , USA.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Sweeney
authors.affiliation: Division of Rheumatology, Allergy and Immunology , UC San Diego School of Medicine , La Jolla, California , USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.affiliation: Department of Nutritional Sciences , Dell Pediatric Research Institute, University of Texas at Austin , Austin, Texas , USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lodi
authors.affiliation: Department of Nutritional Sciences , Dell Pediatric Research Institute, University of Texas at Austin , Austin, Texas , USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Division of Rheumatology, Allergy and Immunology , UC San Diego School of Medicine , La Jolla, California , USA.
authors.forename: David
authors.initials: D
authors.lastname: Boyle
authors.affiliation: Department of Nutritional Sciences , Dell Pediatric Research Institute, University of Texas at Austin , Austin, Texas , USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tiziani
authors.affiliation: Division of Rheumatology, Allergy and Immunology , UC San Diego School of Medicine , La Jolla, California , USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Guma
keywords: Inflammation; Lipids; Rheumatoid Arthritis; Treatment