The N-glycosylation of immunoglobulin G as a novel biomarker of Parkinson's disease

Abstract

The use of the emerging "omics" technologies for large scale population screening is promising in terms of predictive, preventive and personalized medicine. For Parkinson's disease, it is essential that an accurate diagnosis is obtained and disease progression can be monitored. Immunoglobulin G (IgG) has the ability to exert both anti-inflammatory and pro-inflammatory effects, and the N-glycosylation of the fragment crystallizable portion of IgG is involved in this process. This study aimed to determine whether the IgG glycome could be a candidate biomarker for Parkinson's disease. Ninety-four community-based individuals with Parkinson's disease and a sex-, age- and ethnically-matched cohort of 102 individuals with mixed phenotypes, representative of a "normally" aged Caucasian controls, were investigated. Plasma IgG glycans were analyzed by ultra-performance liquid chromatography. Overall, seven glycan peaks and 11 derived traits had statistically significant differences (P < 8.06 × 10-4) between Parkinson's disease cases and healthy controls. Out of the seven significantly different glycan peaks, four were selected by Akaike's Information Criterion to be included in the logistic regression model, with a sensitivity of 87.2% and a specificity of 92.2%. The study suggested that there may be a reduced capacity for the IgG to inhibit Fcγ-RIIIa binding, which would allow an increased ability for the IgG to cause antibody-dependent cell cytotoxicity and a possible state of low-grade inflammation in individuals with Parkinson's disease.

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

“…Two explanations could have been proposed for this surprising finding: either, enzymes encoded by FUT3/FUT6 locus exhibit non-canonical activity of core fucosylation, or that some IgG glycans actually do contain antennary fucose. Recently, the latter was demonstrated in work by Russell et al [14]. Our work does not show any evince for association between FUT3/FUT6 locus and core fucosylation, hence providing an independent evidence that explanation of association between FUT3/FUT6 and IgG glycosylation is rooted in presence of antennary fucose on some IgG glycans.…”

Glycomics for Type 2 Diabetes Biomarker Discovery: Promise of Immunoglobulin G Subclass-Specific Fragment Crystallizable N-glycosylation in the Uyghur Population

“…''Population Glycomics'' is one of the new and emerging approaches to biomarker discovery for common complex diseases. For example, studies in various world populations have found changes in IgG glycosylation in relation to, for example, metabolic syndrome (Lu et al, 2011), lung cancer (Chen et al, 2013), colorectal cancer (Vuckovic et al, 2016), Parkinson's disease (Russell et al, 2017), hypertension (Liu et al, 2018b), and T2DM (Lemmers et al, 2017). Itoh et al (2007) reported minute increments in an N-glycan with a1,6core-fucose within the total N-glycome that was associated with T2DM.…”

Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for Common Chronic Diseases

“…The continuous variables included age (Kristic et al, 2014;Yu et al, 2016) and BMI (Nikolac et al, 2014;Russell et al, 2019), and the categorical variables included hypertension (HT) (Wang et al, 2016), type 2 diabetes (T2D) (Lemmers et al, 2017), dyslipidemia (DL) (Liu et al, 2018a), cardiovascular disease risk score (CDRS) (Menni et al, 2018), ischemic stroke (IS) (Liu et al, 2018b), Parkinson's disease (PD) (Russell et al, 2017), nonalcoholic fatty liver disease (NAFLD) (Zhao et al, 2018), ulcerative colitis (UC) (Trbojevic et al, 2015), Crohn's disease (CD) (Trbojevic et al, 2015), systemic lupus erythematosus (SLE) (Vuckovic et al, 2015), rheumatoid arthritis (RA) (Gudelj et al, 2018b;Sebastian et al, 2016), chronic kidney disease (CKD) (Barrios et al, 2016), and colorectal cancer (CRC) (Vuckovic et al, 2016).…”