O-Glycosylation patterns in post-viral fatigue syndrome: Sialic acid-preserving chemical release

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex inflammatory condition characterized by chronic fatigue, post-exertional malaise, and immune dysregulation whose underlying mechanisms remain poorly understood. Glycosylation, the process of attaching glycans to proteins and lipids, plays a crucial role in immune cell communication and inflammation. As sialic acid has great importance in autoimmune and inflammatory diseases, the focus was directed towards a controlled release and labelling reaction with all conditions avoiding acidic hydrolysis of sialic acid. O-glycan from blood sera and purified antibodies where methyl amidated to stabilize sialic acid. The release reaction proceeds via non-reductive β-elimination and subsequent labelling with a fluorescent compound in conditions able to conserve sialic acid in antennary position. The O-glycan profiles are analyzed by HPLC with fluorescence and MALDI mass spectrometry. O-glycosylation profiles with intact sialylation of ME/CFS patients and healthy controls reveal an altered O-Glycan pattern which may contribute to the chronic inflammatory state observed in ME/CFS.