Cytokine genes as potential biomarkers for muscle weakness in OPMD

Molecular biomarkers emerge as an accurate diagnostic tool, but are scarce for myopathies. Lack of outcome measures sensitive to disease onset and symptom severity hamper evaluation. Cytokines are circulating immunogenic molecules, and their potential as biomarkers has been exploited in the last decade. Cytokines are released from many tissues, including skeletal muscles, but their application to monitor muscle pathology is sparse. We reported that the cytokine functional group is altered in the transcriptome of Oculopharyngeal muscular dystrophy (OPMD). OPMD is a dominantly inherited, late-onset myopathy, caused by an alanine-expansion mutation in the gene encoding for Poly(A) binding protein nuclear 1 (expPABPN1). Here we investigated the hypothesis that cytokines could mark OPMD disease state. We determined cytokines levels in Vastus lateralis muscle from genetically-confirmed expPABPN1 carriers at a symptomatic or pre-symptomatic stage. We identified cytokine-related genes candidates from a transcriptome study in a mouse overexpressing mutant PABPN1. Six cytokines were found to be consistently down-regulated in OPMD Vastus lateralis muscles. Expression levels of these cytokines were highly correlated in controls, but this correlation pattern was disrupted in OPMD. The levels of these six cytokines were not altered in expPABPN1 carriers at a pre-symptomatic stage, suggesting that this group of cytokines and is a potential biomarker for muscle weakness in OPMD. Correlation pattern of expression levels could be a novel measurer for disease state. Molecular Epidemiolog