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

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.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.

DOI: 10.1038/s41467-017-00662-w

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Cite this paper

@inproceedings{Wang2017AMT, title={A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis}, author={Jing Wang and Wei-na Gao and Rudolf Grimm and Shibo Jiang and Yong Liang and Hua Ye and Zhan-guo Li and L Z Yau and Hao Huang and Ju Liu and Min Jiang and Qiong Meng and Tian-Tian Tong and Hai-Hui Huang and Stephanie P Lee and Xing Zeng and Liang Liu and Zhi-Hong Jiang}, booktitle={Nature communications}, year={2017} }