Increased Sialylation of N- and O-Glycans on Serum Maackia amurensis Lectin II Binding Glycoproteins in Autistic Spectrum Disorder

Background: The pathophysiology of Autistic Spectrum Disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. In our previous study we found that expression of serum Siaα2-3 Gal/ GalNAc recognized by Maackia amurensis Lectin II (MAL-II) as well as MAL-II Binding Glycoproteins (MBGs) were significantly increased in ASD compared to Typically Developing (TD) children; however the specific glycoforms of MBGs remain unclear. Method: In this study, N- and O-glycans on sera MAL-II binding glycoproteins (MBGs) from 60 children with ASD and 60 age-matched TD children were profiled by using lectin-magnetic particle conjugate assisted MALDI-TOF/ TOF-MS analysis. Results: A total of 16 representative N-glycans including high-mannose, complex and hybrid, bi-/tri-antennary structures and bisecting GlcNAc glycoforms and 20 representative O-glycans derived from core structures 1, 2, 3, and 4 were annotated in TD and ASD sera. Among these, 6 sialylated or disialylated N-glycans were specifically observed in ASD sera, such as disialylated bi-antennary complex N-glycan (m/z 2061.356). The proportion of total sialylated and disialylated O-glycans were also apparently increased in ASD (63.2% and 15.8%) vs. TD (50.5% and 10.0%) sera respectively, which was most obvious in core 3 and 4 (e.g., sialylated monofucosylated core 4 [m/z 1470.358]). Conclusion: This study can facilitate the discovery of specific sialylated glycans of MBGs that might have much higher sensitivity and specificity as serum biomarkers for ASD diagnosis of children at the earliest age, which might also provide pivotal information for understanding the pathogenesis of ASD.