Serum And Muscular Kl-6/Muc1 Are Useful Biomarker For Gne-Myopathy

Introduction: GNE-myopathy is an autosomal recessive myopathy with distal muscle weakness and the formation of rimmed vacuoles (RVs). Mutations in GNE result in the decrease of sialic acid that is necessary for glycosylation of MUC1. The extracellular domain of MUC1 has the highly glycosylated tandem repeat domain containing precursor of sialylated carbohydrate antigen KL-6. In this study, we examined KL-6/MUC1 in muscle, serum, and fibroblasts. Materials and methods: The muscle biopsy specimens and laboratory data of GNE-myopathy (n = 6), sporadic inclusion body myositis (sIBM; n = 12), polymyositis (PM: n = 8), and normal control (NC: n = 5) were examined. These specimens were subjected to immunohistochemistry, immunofluorescent technique, and western blot analysis. Fibroblasts from two GNE-myopathy patients cultured with or without ManNAc were also examined by western blot analysis. Results: In GNE-myopathy, inclusions and RVs were immunopositive for pTDP-43, MUC1 and KL-6, but the sarcolemma was not. On the other hand, the sarcolemma was also immunopositive for MUC1 and KL-6 in sIBM. In PM and NC, the pale immunoreactivity for MUC1 and KL-6 was observed in the sarcolemma and cytoplasm. Western blot demonstrated the decrease of MUC1 and KL-6 in the skeletal muscle of GNE-myopathy. Serum KL-6 levels of GNE myopathy patients were lower than those of other neuromuscular disease patients (p < 0.05). Fibroblasts showed the increase of MUC1-C and KL-6 according to ManNAc treatment (p < 0.03). Conclusion: This study suggests that the decrease of KL-6/MUC1 reflects the hypoglycosylation as pathogenesis of GNE-myopathy. Serum and muscular KL-6/MUC1 might be a useful biomarker for GNE-myopathy.