title: Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy.
abstract: OBJECTIVE
  The exact pathomechanism of GNE myopathy remains elusive, but likely involves aberrant sialylation. We explored sialylation status of blood-based glycans as potential disease markers.
  
  
  METHODS
  We employed immunoblotting, lectin histochemistry and mass spectrometry.
  
  
  RESULTS
  GNE myopathy muscle showed hyposialylation of predominantly O-linked glycans. The O-linked glycome of patients' plasma compared with controls showed increased amounts of desialylated Thomsen-Friedenreich (T)-antigen, and/or decreased amounts of its sialylated form, ST-antigen. Importantly, all patients had increased T/ST ratios compared with controls. These ratios were normalized in a patient treated with intravenous immunoglobulins as a source of sialic acid.
  
  
  CONCLUSIONS
  GNE myopathy clinical trial data will reveal whether T/ST ratios correlate to muscle function.
  
  
  CONCLUSIONS
  Plasma T/ST ratios are a robust blood-based biomarker for GNE myopathy, and may also help explain the pathology and course of the disease.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Petcharat
authors.initials: P
authors.lastname: Leoyklang
authors.forename: May Christine
authors.initials: MC
authors.lastname: Malicdan
authors.forename: Tal
authors.initials: T
authors.lastname: Yardeni
authors.forename: Frank
authors.initials: F
authors.lastname: Celeste
authors.forename: Carla
authors.initials: C
authors.lastname: Ciccone
authors.forename: Xueli
authors.initials: X
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Nuria
authors.initials: N
authors.lastname: Carrillo-Carrasco
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000097:blood; D009097:Multienzyme Complexes / Q000378:metabolism*; D009135:Muscular Diseases / Q000097:blood* / Q000201:enzymology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000097:blood; D011134:Polysaccharides / Q000097:blood
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D015415:Biomarkers; D037102:Lectins; D009097:Multienzyme Complexes; D019006:Neural Cell Adhesion Molecules; D011134:Polysaccharides; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; C016467:Thomsen-Friedenreich antigen; D019158:N-Acetylneuraminic Acid
keywords: L–MS/MS; N-acetylmannosamine (ManNAc); ST-antigen; core 1 O-linked glycan; glycosylation; hereditary inclusion body myopathy; lectin; sialic acid