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Diagnostic properties of metabolic perturbations in rheumatoid arthritis
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Department of Medicinal Chemistry, BMC, Uppsala University, SE-75123 Uppsala, Sweden. (AcureOmics, Tvistevägen 48, SE-90736 Umeå, Sweden)
AcureOmics, Tvistevägen 48, SE-90736 Umeå, Sweden.
Active Biotech Research, Scheelevägen 22, SE-22007 Lund, Sweden.
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2011 (English)In: Arthritis Research & Therapy, ISSN 1478-6362, Vol. 13, no 1, R19- p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).

Place, publisher, year, edition, pages
2011. Vol. 13, no 1, R19- p.
National Category
Rheumatology and Autoimmunity Medicinal Chemistry
Research subject
URN: urn:nbn:se:umu:diva-40411DOI: 10.1186/ar3243PubMedID: 21303541OAI: diva2:399596
Available from: 2011-02-23 Created: 2011-02-23 Last updated: 2012-09-14Bibliographically approved
In thesis
1. Metabolic variation in autoimmune diseases
Open this publication in new window or tab >>Metabolic variation in autoimmune diseases
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Metabolisk variation i autoimmuna sjukdomar
Abstract [en]

The human being and other animals contain immensely complex biochemical processes that govern their function on a cellular level. It is estimated that several thousand small molecules (metabolites) are produced by various biochemical pathways in humans. Pathological processes can introduce perturbations in these biochemical pathways which can lead to changes in the amounts of some metabolites.Developments in analytical chemistry have made it possible measure a large number metabolites in a single blood sample, which gives a metabolic profile. In this thesis I have worked on establishing and understanding metabolic profiles from patients with rheumatoid arthritis (RA) and from animal models of the autoimmune diseases diabetes mellitus type 1 (T1D) and RA.Using multivariate statistical methods it is possible to identify differences between metabolic profiles of different groups. As an example we identified differences between patients with RA and healthy volunteers. This can be used to elucidate the biochemical processes that are active in a given pathological condition.Metabolite concentrations are affected by a many other things than the presence or absence of a disease. Both genomic and environmental factors are known to influence metabolic profiles. A main focus of my work has therefore been on finding strategies for ensuring that the results obtained when comparing metabolic profiles were valid and relevant. This strategy has included repetition of experiments and repeated measurement of individuals’ metabolic profiles in order to understand the sources of variation.Finding the most stable and reproducible metabolic effects has allowed us to better understand the biochemical processes seen in the metabolic profiles. This makes it possible to relate the metabolic profile differences to pathological processes and to genes and proteins involved in these.The hope is that metabolic profiling in the future can be an important tool for finding biomarkers useful for disease diagnosis, for identifying new targets for drug design and for mapping functional changes of genomic mutations. This has the potential to revolutionize our understanding of disease pathology and thus improving health care.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2012. 47 p.
Rheumatoid Arthritis, Diabetes Mellitus type 1, Metabolic Profiling, Metabolomics, Chemometrics, Multivariate Data Analysis, Mass Spectrometry
National Category
Natural Sciences
Research subject
biological chemistry
urn:nbn:se:umu:diva-59475 (URN)978-91-7459-480-5 (ISBN)
Public defence
2012-10-05, KBC-huset, Lilla hörsalen (KB3A9), Umeå universitet, Umeå, 10:00 (English)
Available from: 2012-09-14 Created: 2012-09-14 Last updated: 2012-09-14Bibliographically approved

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Madsen, Rasmus KirkegaardAlenius, Gerd-MarieRantapää-Dahlqvist, SolbrittTrygg, Johan
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