| An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spectroscopy. | |
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MedLine Citation:
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PMID: 17696462 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rheumatoid arthritis, a debilitating, systemic inflammatory joint disease, is likely accompanied by alterations in circulating metabolites. Here, an 1H NMR spectroscopy-based metabolomics approach was developed to establish a metabolic 'biomarker pattern' in a model of rheumatoid arthritis, the K/BxN transgenic mouse. Sera obtained from arthritic K/BxN mice (N = 15) and a control population (N = 19) having the same genetic background, but lacking the arthritogenic T-cell receptor KRN transgene, were compared by 1H NMR spectroscopy. A unique method was developed by combining technologies such as ultrafiltration to remove proteins from serum samples, quantitative 'targeted profiling' of known metabolites, pseudo-quantitative profiling of unknown resonances, a supervised O-PLS-DA pattern recognition analysis, and a metabolic-pathway based network analysis for interpretation of results. In total, 88 spectral features were profiled (59 metabolites and 28 unknown resonances). A highly significant subset of 18 spectral features (15 known compounds and 3 unknown resonances) was identified (p = 0.00075 using MANOVA) that we term a 'metabolic bioprofile'. We identified metabolites relating to nucleic acid, amino acid, and fatty acid metabolism, as well as lipolysis, reactive oxygen species generation, and methylation. Pathway analysis suggested a shift from metabolites involved in numerous reactions (hub-metabolites) toward intermediates and metabolic endpoints associated with arthritis. The results attest to the metabolic complexity of systemic inflammation and to the power of the experimental approach for identifying a wide variety of disease-associated marker candidates. The diagnostic and prognostic implications of monitoring a spectrum of metabolic events simultaneously using serum samples is discussed with respect to the potential for individualized medicine. |
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Authors:
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Aalim M Weljie; Reza Dowlatabadi; B Joan Miller; Hans J Vogel; Frank R Jirik |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-08-15 |
Journal Detail:
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Title: Journal of proteome research Volume: 6 ISSN: 1535-3893 ISO Abbreviation: J. Proteome Res. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-09-07 Completed Date: 2007-11-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101128775 Medline TA: J Proteome Res Country: United States |
Other Details:
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Languages: eng Pagination: 3456-64 Citation Subset: IM |
Affiliation:
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Metabolomics Research Centre, Department of Biological Sciences, Department of Biochemistry and Molecular Biology, and the McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta T2N 4N1, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arthritis / blood*, diagnosis*, metabolism* Arthritis, Rheumatoid / blood* Biological Markers / chemistry* Crosses, Genetic Disease Models, Animal Inflammation / blood* Magnetic Resonance Spectroscopy / methods* Mice Mice, Inbred C57BL Mice, Transgenic Proteomics / methods* |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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