title: Cytokine genes as potential biomarkers for muscle weakness in OPMD.
abstract: 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 of therapeutic developments. 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 report that the cytokine functional group is altered in the transcriptome of oculopharyngeal muscular dystrophy (OPMD). OPMD is a dominant, 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 the vastus lateralis muscle from genetically confirmed expPABPN1 carriers at a symptomatic or a presymptomatic stage. We identified cytokine-related genes candidates from a transcriptome study in a mouse overexpressing exp 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 6 cytokines were not altered in expPABPN1 carriers at a pre-symptomatic stage, suggesting that this group of cytokines is a potential biomarker for muscle weakness in OPMD. Correlation pattern of expression levels could be a novel measurer for disease state.
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Muhammad
authors: M
authors: Riaz
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Yotam
authors: Y
authors: Raz
authors: Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Barbara
authors: B
authors: van der Slujis
authors: School of Biological Sciences, Royal Holloway - University of London, Egham, Surrey TW20 0EX, UK.
authors: George
authors: G
authors: Dickson
authors: Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Baziel
authors: B
authors: van Engelen
authors: Department of Neurology, Rigshospitalet, Copenhagen Neuromuscular Center, University of Copenhagen, Denmark.
authors: John
authors: J
authors: Vissing
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands v.raz@lumc.nl.
authors: Vered
authors: V
authors: Raz
mesh_terms: D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D051379:Mice; D039141:Muscular Dystrophy, Oculopharyngeal / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D057089:Pathology, Molecular; D039122:Poly(A)-Binding Protein I / Q000096:biosynthesis / Q000235:genetics*; D052097:Quadriceps Muscle / Q000473:pathology; D059467:Transcriptome / Q000235:genetics*
chemical_list: D015415:Biomarkers; D016207:Cytokines; C576588:PABPN1 protein, human; D039122:Poly(A)-Binding Protein I