Glycan Biomarkers for Rheumatoid Arthritis and Its Remission Status in Han Chinese Patients

Abstract

Rheumatoid arthritis (RA), a systemic, chronic, and progressive inflammatory autoimmune disease, affects up to 1.0% of the world population doubling mortality rate of patients and is a major global health burden. Worrisomely, we lack robust diagnostics of RA and its remission status. Research with the next-generation biomarker technology platforms such as glycomics offers new promises in this context. We report here a clinical case-control study comprising 128 patients suffering from chronic RA (80.22% in remission, 19.78% active clinically) and 195 gender- and age-matched controls, with a view to the putative glycan biomarkers of RA as well as its activity or remission status in Han Chinese RA patients. Hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC) was used for the analysis of IgG glycans. The regression model identified the glycans that predict RA status, while a receiver operating characteristic (ROC) curve analysis validated the sensitivity and prediction power. Among the total 24 glycan peaks (GP1-GP24), ROC analysis showed only GP1 prediction to be highly sensitive with an area under the curve (AUC) = 0.881. Even though GP21 and GP22 could predict active status among the RA cases (p < 0.05), they had lower sensitivity of prediction with an AUC = 0.658. Taken together, these observations suggest that GP1 might have potential as a putative biomarker for RA in the Han Chinese population, while the change in IgG glycosylation shows association with the RA active and remission states. To the best of our knowledge, this is the first glycomics study with respect to disease activity and remission states in RA.

Reduced sialyl-Lewisxon salivary MUC7 from patients with burning mouth syndrome

“…20 Glycosylation changes have been investigated in conditions such as aphthous stomatitis, inflammation and cancer. 16,26 Altered terminal sugar residue may have regulatory functions and confer biological consequences, which might be the case also in BMS patients. The reduction in the Si-Le x could result in reduced ability in clearing the bacteria from the oral cavity.…”

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).…”

Next-Generation (Glycomic) Biomarkers for Cardiometabolic Health: A Community-Based Study of Immunoglobulin G N-Glycans in a Chinese Han Population

“…Glycans participate in substantive intercellular and intracellular functions, such as protein quality control, cell adhesion, cell-cell recognition, signal transduction, cell proliferation, and cell differentiation (Brown et al, 2007;Varki, 1993Varki, , 2017Wang et al, 2016a). Given that almost all mammalian cells are covered with glycans (Apweiler et al, 1999), it is not a surprise that protein glycosylation is involved in the pathophysiology of many human diseases, such as cancer (Adamczyk et al, 2012;Wang, 2013), congenital disorders of glycosylation (Grünewald et al, 2002), autoimmune disease (Keser et al, 2017;Sebastian et al, 2016), and inflammatory diseases (Adua et al, , 2019Theodoratou et al, 2014).…”

“…N-glycans attach to the conserved asparagine 297 of both heavy chains in the fragment crystallizable region of IgG and act as a switch between proinflammatory and anti-inflammatory responses of IgG (Gornik et al, 2012;Jefferis, 2009). Changes to the IgG Nglycan profiles are involved in several inflammatory diseases, such as hypertension (Gao et al, 2017;Liu et al, 2018c;Wang et al, 2016b), stroke (Liu et al, 2018b), T2DM (Ge et al, 2018;Lemmers et al, 2017), Parkinson's disease , and rheumatoid arthritis (Sebastian et al, 2016).…”