Sialylation of Thomsen–Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy. (June 2014)

• Record Type: Journal Article
• Authors: Leoyklang, Petcharat; Malicdan, May Christine; Yardeni, Tal; Celeste, Frank; Ciccone, Carla; Li, Xueli; Jiang, Rong; Gahl, William A; Carrillo-Carrasco, Nuria; He, Miao; Huizing, Marjan
• Is Part Of: Biomarkers in medicine. Volume 8:Number 5(2014)
• Page Start: 641
• Page End: 652
• Publication Date: 2014-06
• Subjects: core 1 O-linked glycan -- glycosylation -- hereditary inclusion body myopathy -- lectin -- L–MS/MS -- N-acetylmannosamine (ManNAc) -- sialic acid -- ST-antigen; Biochemical markers -- Periodicals; 610.28
• DOI: 10.2217/bmm.14.2
• Languages: English
• ISSNs: 1752-0363

Abstract

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.