Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia

Kim Jones, Terri Gelbart, Thomas C. Whisenant, Jill Waalen, Tony S. Mondala, David N. Iklé, Daniel R. Salomon, Robert (Rob) Bennett, Sunil M. Kurian

    Research output: Contribution to journalArticle

    11 Scopus citations

    Abstract

    Objective. Fibromyalgia (FM) is a common pain disorder characterised by nociceptive dysregulation. The basic biology of FM is poorly understood. Herein we have used agnostic gene expression as a potential probe for informing its underlying biology and the development of a proof-of-concept diagnostic gene expression signature. Methods. We analysed RNA expression in 70 FM patients and 70 healthy controls. The isolated RNA was amplified and hybridised to Affymetrix® Human Gene 1.1 ST Peg arrays. The data was analysed using Partek Genomics Suite v. 6.6. Results. Fibromyalgia patients exhibited a differential expression of 421 genes (p<0.001), several relevant to pathways for pain processing, such as glutamine/glutamate signaling and axonal development. There was also an upregulation of several inflammatory pathways and downregulation of pathways related to hypersensitivity and allergy. Using rigorous diagnostic modeling strategies, we show "locked" gene signatures discovered on Training and Test cohorts, that have a mean Area Under the Curve (AUC) of 0.81 on randomised, independent external data cohorts. Lastly, we identified a subset of 10 probesets that provided a diagnostic sensitivity for FM of 95% and a specificity of 96%. We also show that the signatures for FM were very specific to FM rather than common FM comorbidities. Conclusion. These findings provide new insights relevant to the pathogenesis of FM, and provide several testable hypotheses that warrant further exploration and also establish the foundation for a first blood-based molecular signature in FM that needs to be validated in larger cohorts of patients.

    Original languageEnglish (US)
    Pages (from-to)89-98
    Number of pages10
    JournalClinical and Experimental Rheumatology
    Volume34
    StatePublished - 2016

    Keywords

    • Diagnostic signature
    • Fibromyalgia
    • Gene expression
    • Pathophysiology
    • Phenotype

    ASJC Scopus subject areas

    • Medicine(all)

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  • Cite this

    Jones, K., Gelbart, T., Whisenant, T. C., Waalen, J., Mondala, T. S., Iklé, D. N., Salomon, D. R., Bennett, R. R., & Kurian, S. M. (2016). Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia. Clinical and Experimental Rheumatology, 34, 89-98.