Abnormal variation of serum N-glycan on Bechet’s disease: tracing the structural isomeric distribution

다국어 초록 (Multilingual Abstract)

Bechet’s disease (BD) is an immune disease which showed a chronic and relapsing systemic vasculitis
of unknown etiology. It is characterized by recurrent ulcers and inflammations on oral, genital, uvea
area and further vascular, central nervous system (CNS), and gastrointestinal tracks. Bechet’s disease has
a wide spectrum of symptoms ranging from benign episodes to more serious complications such as
blindness. Although many diagnostic criteria have been developed and revised by experts in the field,
diagnosing BD is still complicated and challenging. To discover the diagnostic biomarkers, serum
N-glycans from Bechet patient (n=100) and healthy control (n=100) have been compared. Instead of
conventional global profiling of serum N-glycome, quantitative ratio between structural isomers were
analyzed by UPLC-triple quadruple mass spectrometry. Three acidic glycans with the composition of
5:4:0:1, 5:4:0:2, and 5:4:1:1 (Hex:HexNAc:Fuc:NeuAc) were monitored in MRM mode, then six, two
and three isomers were found, respectively. Among eleven bi-antennary glycan isomers, four of them
showed high diagnostic efficacy having AUC of ROC curve over 0.98. When the sensitivity was fixed
to 90%, corresponding specificities were over 92% to 96%. Another four isomers showed the AUC
from 0.84 to 0.94 showing 64%~84% specificity with the sensitivity of 90%. Marker glycans exhibits
unique correlations with biological characteristics of cohorts. Two isomers of 5:4:0:1 and one of 5:4:0:2
isomer were able to completely distinguish male and female groups in healthy control cohort. Glycan
expression level in female groups were 6 to 10 times higher than those observed in male groups
resulting 1.0 AUC in ROC curve. Expression level in patient cohort were 5 to 10-folds higher than
those in control group showing complete segregation. Correlation between the glycans were also clear.
Groups of isomers with each composition exhibits Pearson’s product over ±0.90 within or between the
groups. This study present the novel approach for the disease marker discovery that tracing the isomeric
structure of specific N-glycan. As results, the markers with undoubtable quantitative deviation and the
correlations reflecting their biological characteristics have been found.