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

Author

Listed:
  • Jing-Rong Wang

    (Macau University of Science and Technology
    Macau University of Science and Technology)

  • Wei-Na Gao

    (Macau University of Science and Technology
    Macau University of Science and Technology)

  • Rudolf Grimm

    (Agilent Technologies)

  • Shibo Jiang

    (Fudan University
    New York Blood Center)

  • Yong Liang

    (Macau University of Science and Technology
    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
    Macau University of Science and Technology)

  • Hao Huang

    (Macau University of Science and Technology
    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
    Macau University of Science and Technology)

  • Tian-Tian Tong

    (Macau University of Science and Technology
    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
    Macau University of Science and Technology)

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.

Suggested Citation

  • 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 L, 2017. "A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00662-w
    DOI: 10.1038/s41467-017-00662-w
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