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20-09-2017 | Rheumatoid arthritis | Article

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

Journal:
Nature Communications

Authors: Jing-Rong Wang, Wei-Na Gao, Rudolf Grimm, Shibo Jiang, Yong Liang, Hua Ye, Zhan-Guo Li, Lee-Fong Yau, Hao Huang, Ju Liu, Min Jiang, Qiong Meng, Tian-Tian Tong, Hai-Hui Huang, Stephanie Lee, Xing Zeng, Liang Liu, Zhi-Hong Jiang

Publisher: Nature Publishing Group UK

Abstract

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.

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