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

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 () and Zhi-Hong Jiang ()
Additional contact information
Jing-Rong Wang: Macau University of Science and Technology
Wei-Na Gao: Macau University of Science and Technology
Rudolf Grimm: Agilent Technologies
Shibo Jiang: Fudan University
Yong Liang: Macau University of Science and Technology
Hua Ye: Peking University People’s Hospital
Zhan-Guo Li: Peking University People’s Hospital
Lee-Fong Yau: Macau University of Science and Technology
Hao Huang: Macau University of Science and Technology
Ju Liu: Jiujiang First People’s Hospital
Min Jiang: Jiujiang First People’s Hospital
Qiong Meng: Macau University of Science and Technology
Tian-Tian Tong: Macau University of Science and Technology
Hai-Hui Huang: Macau University of Science and Technology
Stephanie Lee: Agilent Technologies Hong Kong Ltd.
Xing Zeng: Guangdong Provincial Hospital of Chinese Medicine
Liang Liu: Macau University of Science and Technology
Zhi-Hong Jiang: Macau University of Science and Technology

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00662-w

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