Multiplex Screen of Serum Biomarkers in Facioscapulohumeral Muscular Dystrophy.

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 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.