Change search
ReferencesLink to record
Permanent link

Direct link
Metabolic responses to change in disease activity during tumor necrosis factor inhibition in patients with rheumatoid arthritis
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
AcureOmics AB, Tvistevägen 48, 907 36 Umeå, Sweden.
Umeå Plant Science Center, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, SE-90183 Umeå, Sweden.
Show others and affiliations
2012 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 11, no 7, 3796-3804 p.Article in journal (Refereed) Published
Abstract [en]

Assessment of disease activity in patients with rheumatoid arthritis (RA) is of importance in the evaluation of treatment. The most important measure of disease activity is the Disease Activity Score counted in 28 joints (DAS28). In this study, we evaluated whether metabolic profiling could complement current measures of disease activity. Fifty-six patients, in two separate studies, were followed for two years after commencing anti-TNF therapy. DAS28 was assessed, and metabolic profiles were recorded at defined time points. Correlations between metabolic profile and DAS28 scores were analyzed using multivariate statistics. The metabolic responses to lowering DAS28 scores varied in different patients but could predict DAS28 scores at the individual and subgroup level models. The erythrocyte sedimentation rate (ESR) component in DAS28 was most correlated to the metabolite data, pointing to inflammation as the primary effect driving metabolic profile changes. Patients with RA had differing metabolic response to changes in DAS28 following anti-TNF therapy. This suggests that discovery of new metabolic biomarkers for disease activity will derive from studies at the individual and subgroup level. Increased inflammation, measured as ESR, was the main common effect seen in metabolic profiles from periods associated with high DAS28.

Place, publisher, year, edition, pages
2012. Vol. 11, no 7, 3796-3804 p.
Keyword [en]
anti-TNF treatment; rheumatoid arthritis; OPLS; metabolomics
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
URN: urn:nbn:se:umu:diva-56546DOI: 10.1021/pr300296vPubMedID: 22574709OAI: diva2:535716
Available from: 2012-06-20 Created: 2012-06-20 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

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Madsen, Rasmus KirkegaardRantapää-Dahlqvist, SolbrittTrygg, Johan
By organisation
Department of ChemistryReumatology
In the same journal
Journal of Proteome Research
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 301 hits
ReferencesLink to record
Permanent link

Direct link