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

• Type of Material: Article
• Authors: Petcharat Leoyklang, National Human Genome Research Institute; May Christine Malicdan, National Human Genome Research Institute; Tal Yardeni, National Human Genome Research Institute; Frank Celeste, National Institutes of Health; Carla Ciccone, National Human Genome Research Institute; Xueli Li, Emory University; Rong Jiang, Emory University; William A. Gahl, National Human Genome Research Institute; Nuria Carrillo-Carrasco, National Institutes of Health; Miao He, Emory University; Marjan Huizing, National Human Genome Research Institute
• Language: English
• Date: 2014-06-01
• Publisher: Future Medicine
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Future Medicine Ltd.
• Final Published Version (URL): http://dx.doi.org/10.2217/BMM.14.2
• Title of Journal or Parent Work: Biomarkers in Medicine
• ISSN: 1752-0363
• Volume: 8
• Issue: 5
• Start Page: 641
• End Page: 652
• Grant/Funding Information: This study was supported by the Intramural Research Program of the National Human Genome Research Institute (NHGRI) and the Therapeutics for Rare and Neglected Diseases (TRND) Program of the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Bethesda, Maryland, United States.
• Keywords: N-acetylmannosamine (ManNAc); lectin; N-GLYCAN; Medicine, Research & Experimental; MASS-SPECTROMETRY; Life Sciences & Biomedicine; SINGLE PATIENT RESPONSE; RIMMED VACUOLES; sialic acid; L-MS/MS; core 1 O-linked glycan; CONGENITAL DISORDERS; Research & Experimental Medicine; CELL-ADHESION MOLECULE; ACID BIOSYNTHESIS; Science & Technology; ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; INCLUSION-BODY MYOPATHY; hereditary inclusion body myopathy; ST-antigen; glycosylation; DISTAL MYOPATHY
• Research Categories: Health Sciences, Pathology; Biology, Genetics

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.