A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis

• Published in: Nature communications Vol. 8; no. 1; pp. 631 - 14
• Main Authors: Wang, Jing-Rong, Gao, Wei-Na, Grimm, Rudolf, Jiang, Shibo, Liang, Yong, Ye, Hua, Li, Zhan-Guo, Yau, Lee-Fong, Huang, Hao, Liu, Ju, Jiang, Min, Meng, Qiong, Tong, Tian-Tian, Huang, Hai-Hui, Lee, Stephanie, Zeng, Xing, Liu, Liang, Jiang, Zhi-Hong
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 20.09.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Abundance; Acetylation; Adult; Aged; Antibodies; Arthritis; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Biomarkers; Biomarkers - metabolism; Case-Control Studies; Citrulline; Drugs; Female; Glycan; Glycoproteins; Glycosylation; Humans; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Infectious diseases; Male; Microfluidics; Middle Aged; N-glycans; Pathogenesis; Patients; Peptides, Cyclic - immunology; Polysaccharides; Polysaccharides - immunology; Polysaccharides - metabolism; Post-translation; Protein Processing, Post-Translational; Rheumatoid arthritis; Rheumatoid factor; Rheumatoid Factor - immunology; Sulfates - immunology; Sulfates - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-00662-w

N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect. Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip. We discover 20 sulfated and 4 acetylated N-glycans on IgGs. Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans. From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients. This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies. Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.