Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy

Biomark Med. 2014;8(5):641-52. doi: 10.2217/bmm.14.2.


Aim: 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.

Discussion: GNE myopathy clinical trial data will reveal whether T/ST ratios correlate to muscle function.

Conclusion: 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.

Keywords: L–MS/MS; N-acetylmannosamine (ManNAc); ST-antigen; core 1 O-linked glycan; glycosylation; hereditary inclusion body myopathy; lectin; sialic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, Tumor-Associated, Carbohydrate / blood*
  • Antigens, Tumor-Associated, Carbohydrate / metabolism*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Humans
  • Lectins / blood
  • Multienzyme Complexes / metabolism*
  • Muscular Diseases / blood*
  • Muscular Diseases / enzymology*
  • N-Acetylneuraminic Acid / metabolism*
  • Neural Cell Adhesion Molecules / blood
  • Polysaccharides / blood


  • Antigens, Tumor-Associated, Carbohydrate
  • Biomarkers
  • Lectins
  • Multienzyme Complexes
  • Neural Cell Adhesion Molecules
  • Polysaccharides
  • UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
  • Thomsen-Friedenreich antigen
  • N-Acetylneuraminic Acid