Dataset Information

Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

ABSTRACT:

Objective

The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies.

Methods

In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification.

Results

The questionnaire items 'Red joints', 'Swollen joints', 'Warm joints' suggest differences in the level of inflammation between the groups although c-reactive protein (CRP) and rheumatoid factor (RHF) levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS) levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA) axis function.

Conclusion

Significant and relevant biochemical differences are found between Cold and Heat RA patients. Differences in immune function, HPA axis involvement and muscle breakdown point towards opportunities to tailor disease management strategies to each of the subgroups RA patient.

SUBMITTER: van Wietmarschen HA

PROVIDER: S-EPMC3440441 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

van Wietmarschen Herman A HA Dai Weidong W van der Kooij Anita J AJ Reijmers Theo H TH Schroën Yan Y Wang Mei M Xu Zhiliang Z Wang Xinchang X Kong Hongwei H Xu Guowang G Hankemeier Thomas T Meulman Jacqueline J JJ van der Greef Jan J

PloS one 20120912 9

<h4>Objective</h4>The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies.<h4>Methods</h4>In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In additio ...[more]

PMID: 22984493

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Project description:The disease category of early rheumatoid arthritis (RA) has been limited with respect to clinical criteria. Pathological manifestations of synovitis in patients whose disease is clinically classified as early RA seem to be heterogeneous, with regular variations. To clarify the relation between the molecular and histopathological features of the synovitis, we analyzed gene-expression profiles in the synovial lining tissues to correlate them with histopathological features. Synovial tissues were obtained from knee joints of 12 patients with early RA by targeted biopsy under arthroscopy. Surgical specimens of long-standing RA (from four patients) were examined as positive controls. Each histopathological parameter characteristic of rheumatoid synovitis in synovial tissues was scored under light microscopy. Total RNAs from synovial lining tissues were obtained from the specimens selected by laser capture microdissection and the mRNAs were amplified by bacteriophage T7 RNA polymerase. Their cDNAs were analyzed in a cDNA microarray with 23,040 cDNAs, and the levels of gene expression in multilayered lining tissues, compared with those of normal-like lining tissues in specimens from the same person, were determined to estimate gene-expression profiles characteristic of the synovial proliferative lesions in each case. Based on cluster analysis of all cases, gene-expression profiles in the lesions in early RA fell into two groups. The groups had different expression levels of genes critical for proliferative inflammation, including those encoding cytokines, adhesion molecules, and extracellular matrices. One group resembled synovitis in long-standing RA and had high scores for some histopathological features - involving accumulations of lymphocytes and plasma cells - but not for other features. Possible differences in the histopathogenesis and prognosis of synovitis between the two groups are discussed in relation to the candidate genes and histopathology.

Dataset Information

Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

Objective

Methods

Results

Conclusion

Publications

Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

Similar Datasets

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