Background Contemporary research has revealed a dysfunctional central nervous system as being an important component in the clinical presentation of fibromyalgia (FM). However, the reasons for this dysfunction, are far from clear. One problem in studying fibromyalgia is the lack of a well-defined phenotype. This is a significant problem when attempting to define FM at the genomic level.
Objectives In this study we have employed gene expression methods to define biological markers that could potentially assist in better defining FM genomically.
Methods Global gene expression in 70 fibromyalgia patients and 70 healthy matched controls was analyzed in terms of sensitivity and specificity based on the 1990 American College of Rheumatology definition of FM.
Results The molecular profiling of peripheral blood revealed a differential expression of genes in known pathways for pain processing, such as glutamine/glutamate signaling and axonal development, suggesting a dysregulation of these functions. There was also an upregulation of inflammatory molecules in FM patients and downregulation of specific pathways related to hypersensitivity and allergy. Based on these profiles we identified a panel of candidate gene expression-based classifiers that could help establish an objective molecular diagnostic guide for the design and testing of new therapies for FM. Classifiers of 10-71 probesets showed sensitivity, specificity, PPV, NPV and an AUC as high as 95%, 96%, 95%, 96% and 0.931.
Conclusions The findings reported here provide several new insights relevant to the possible pathogenesis of FM, and provide several testable hypotheses that warrant further exploration.
Acknowledgements This study was funded by NIH grant R21NRO12572
Disclosure of Interest None declared