title: Multiplex Screen of Serum Biomarkers in Facioscapulohumeral Muscular Dystrophy.
abstract: BACKGROUND
  Recent studies have proposed a unified genetic model for Facioscapulohumeral muscular dystrophy (FSHD), identifying potential therapeutic targets for future clinical trials. Serum biomarkers related to disease activity will be important for proof of concept or early phase clinical studies.
  
  
  OBJECTIVE
  To identify potential serum biomarkers in FSHD for possible use in future clinical trials.
  
  
  METHODS
  We performed a prospective cross-sectional study of serum biomarkers in 22 FSHD patients (19 FSHD1, 3 FSHD2) compared to 23 age and gender-matched healthy controls using a commercial multiplex, microsphere-based immune-fluorescent assay of 243 markers (Myriad, Human Discovery MAP 250, v2.0).
  
  
  RESULTS
  169 markers had values sufficient for analysis. Correction for multiple testing identified 7 biomarkers below a 5% false discovery rate: creatine kinase MB fraction (CKMB, 6.52 fold change, P<0.0001), tissue-type plasminogen activator (PLAT, 1.64 fold change, P<0.0001), myoglobin (2.23 fold change, P=0.0001), epidermal growth factor (EGF, 2.33 fold change, P=0.0004), chemokine (C-C motif) ligand 2 (1.48 fold change, P=0.0004), CD 40 ligand (1.89 fold change, P=0.001), and vitronectin (VTN, 1.28 fold change, P=0.001). Moderate correlations to measures of FSHD disease were seen for CKMB, PLAT, and EGF. Markers in the plasminogen pathway (PLAT, serpin peptidase inhibitor, and VTN) were correlated with each other in FSHD but not healthy controls.
  
  
  CONCLUSIONS
  Commercial multiplex immune-fluorescent screening is a potentially powerful tool for identifying biomarkers for future FSHD therapeutic trials. Biomarkers identified in this study warrant further study in a larger prospective validation study.
authors.affiliation: Department of Neurology, University of Kansas Medical Center, Kansas City, KS ; Department of Neurology, University of Rochester Medical Center, Rochester, NY.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Statland
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, NY.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Donlin-Smith
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tapscott
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Silvere
authors.initials: S
authors.lastname: van der Maarel
authors.affiliation: Department of Neurology, University of Rochester Medical Center, Rochester, NY.
authors.forename: Rabi
authors.initials: R
authors.lastname: Tawil
keywords: Biomarker; DUX4; Facioscapulohumeral Muscular Dystrophy; Muscle Disease; Proteomics