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.