Open AccessA method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis
Author(s) -
Jingrong Wang,
Weina Gao,
Rudolf Grimm,
Shibo Jiang,
Yong Liang,
Hua Ye,
Zhanguo Li,
Lee-Fong Yau,
Hao Huang,
Ju Liu,
Min Jiang,
Qiong Meng,
Taotao Tong,
Stephanie J. Lee,
Xing Zeng,
Liang Liu,
Zhihong Jiang
Publication year - 2017
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-017-00662-w
Subject(s) - glycan , rheumatoid arthritis , antibody , glycosylation , rheumatoid factor , immunology , glycomics , fragment crystallizable region , biomarker , immunoglobulin g , autoantibody , medicine , computational biology , biology , glycoprotein , microbiology and biotechnology , biochemistry
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.