LC-MS metabolomics of psoriasis patients reveals disease severity-dependent increases in circulating amino acids that are ameliorated by anti-TNFα treatment

Kamleh, Muhammad Anas and Snowden, Stuart G. and Grapov, Dmitry and Blackburn, Gavin J. and Watson, David G. and Xu, Ning and Ståhle, Mona and Wheelock, Craig E. (2015) LC-MS metabolomics of psoriasis patients reveals disease severity-dependent increases in circulating amino acids that are ameliorated by anti-TNFα treatment. Journal of Proteome Research, 14 (1). pp. 557-566. ISSN 1535-3907 (https://doi.org/10.1021/pr500782g)

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Abstract

Psoriasis is an immune-mediated highly heterogeneous skin disease in which genetic as well as environmental factors play important roles. In spite of the local manifestations of the disease, psoriasis may progress to affect organs deeper than the skin. These effects are documented by epidemiological studies, but they are not yet mechanistically understood. In order to provide insight into the systemic effects of psoriasis, we performed a nontargeted high-resolution LC-MS metabolomics analysis to measure plasma metabolites from individuals with mild or severe psoriasis as well as healthy controls. Additionally, the effects of the anti-TNFα drug Etanercept on metabolic profiles were investigated in patients with severe psoriasis. Our analyses identified significant psoriasis-associated perturbations in three metabolic pathways: (1) arginine and proline, (2) glycine, serine and threonine, and (3) alanine, aspartate, and glutamate. Etanercept treatment reversed the majority of psoriasis-associated trends in circulating metabolites, shifting the metabolic phenotypes of severe psoriasis toward that of healthy controls. Circulating metabolite levels pre- and post-Etanercept treatment correlated with psoriasis area and severity index (PASI) clinical scoring (R(2) = 0.80; p < 0.0001). Although the responsible mechanism(s) are unclear, these results suggest that psoriasis severity-associated metabolic perturbations may stem from increased demand for collagen synthesis and keratinocyte hyperproliferation or potentially the incidence of cachexia. Data suggest that levels of circulating amino acids are useful for monitoring both the severity of disease as well as therapeutic response to anti-TNFα treatment.

ORCID iDs

Kamleh, Muhammad Anas, Snowden, Stuart G., Grapov, Dmitry, Blackburn, Gavin J., Watson, David G. ORCID logoORCID: https://orcid.org/0000-0003-1094-7604, Xu, Ning, Ståhle, Mona and Wheelock, Craig E.;
  • Item type:Article
    ID code:60158
    Dates:
    Date
    Event
    2 January 2015
    Published
    31 October 2014
    Published Online
    Notes:This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Journal of Proteome Research, copyright © American Chemical Society after peer review. To access the final edited and published work, see http://pubs.acs.org/doi/10.1021/pr500782g .
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:13 Mar 2017 14:30
    Last modified:11 Nov 2024 11:14
    URI:https://strathprints.strath.ac.uk/id/eprint/60158
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