The N-Glycosylation of Total Plasma Proteins and IgG in Atrial Fibrillation

Abstract

Atrial fibrillation is a disease with a complex pathophysiology, whose occurrence and persistence are caused not only by aberrant electrical signaling in the heart, but by the development of a susceptible heart substrate. These changes, such as the accumulation of adipose tissue and interstitial fibrosis, are characterized by the presence of inflammation. N-glycans have shown great promise as biomarkers in different diseases, specifically those involving inflammatory changes. To assess the changes in the N-glycosylation of the plasma proteins and IgG in atrial fibrillation, we analyzed the N-glycosylation of 172 patients with atrial fibrillation, before and six months after a pulmonary vein isolation procedure, with 54 cardiovascularly healthy controls. An analysis was performed using ultra-high-performance liquid chromatography. We found one oligomannose N-glycan structure from the plasma N-glycome and six IgG N-glycans, mainly revolving around the presence of bisecting N-acetylglucosamine, that were significantly different between the case and control groups. In addition, four plasma N-glycans, mostly oligomannose structures and a derived trait that was related to them, were found to be different in the patients who experienced an atrial fibrillation recurrence during the six-month follow-up. IgG N-glycosylation was extensively associated with the CHA₂DS₂-VASc score, confirming its previously reported associations with the conditions that make up the score. This is the first study looking at the N-glycosylation patterns in atrial fibrillation and warrants further investigation into the prospect of glycans as biomarkers for atrial fibrillation.

Keywords: N-glycosylation; atrial fibrillation; biomarker; immunoglobulin G; pulmonary vein isolation; total plasma proteins.

Figure 1

Statistically significant differences in N-glycan traits in plasma and IgG between the control group and AF group. Data are shown as boxplots, the line represents the median value, the box extends from the 25th to the 75th percentile, and the lines extend to the 1.5 × IQR. Outliers outside 1.5 IQR are plotted individually as dots.

Figure 2

Association of total plasma protein N-glycosylation with AF recurrence (A). Association of IgG N-glycosylation between the pre- and post-procedure measurements (B). Association of IgG N-glycosylation with the CHA₂DS₂-VASc score (C). Data are shown as boxplots, as described in Figure 1. Only statistically significant structures and traits are shown.