Preprint Open Access
Valerie O'Donnell; Nils H Schebb; Ginger L Milne; Michael P Murphy; Christopher P Thomas; Dieter Steinhilber; Stacy G Wendell; Hartmut Kühn; Per-Johan Jakobsson; Ian Blair; Robert C Murphy; Bruce A Freeman; Alan R Brash; Garret FitzGerald
Specialized pro-resolving mediators (SPM) derived from oxygenation of long chain polyunsaturated fatty acids (PUFA) were originally described by Serhan and colleagues and have been proposed as mediators of inflammation resolution. Families of SPM described in the literature include lipoxins, resolvins, maresins, protectins and their peptide conjugates. In this article Gomez and co-authors report that levels of plasma SPM from patients with early rheumatoid arthritis predict response to biologic therapy after 6 months. SPM were measured in this study using liquid chromatography tandem mass spectrometry (LC-MS/MS). On reviewing the methods, supplementary analytical data and the online peer review file, we note several concerns, regarding both analytical methods and experimental conclusions. Specifically, quantifications of multiple SPM are based on weak or absent peaks in ion chromatograms, and mass spectra extracted from the recordings do not concord with authentic standards of SPM molecules presented. Indeed, applying their methodology, it is possible to infer the presence of lipids in clean methanol and buffer blanks. The LC-MS/MS analyses described, which are widely applied to the analysis of SPM, fail to meet the standards of accepted practices in the small molecule and lipidomics field or those endorsed by professional bodies for analytical chemistry. Application of this flawed methodology to SPM analysis brings into question the very occurrence of many of these lipids in biological samples, their proposed impact on inflammatory processes, and biomarker claims.
matters arising preprint.pdf
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