Glycosylated IgG antibodies contribute to the recovery of haemorrhagic fever with renal syndrome patients

糖基化IgG抗体有助于肾综合征出血热患者的康复

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作者:Chuansong Quan # ,Lu Wang #,Jiming Gao #,Yaoni Li #,Xiaoyu Xu #,Houqiang Li,Zixuan Gao,Wenxu Ruan,Hongzhi Liu,Qian Li,Weijia Xing,Liqiong Zhao,Michael J Carr,Weifeng Shi,Haifeng Hou

Abstract

Haemorrhagic fever with renal syndrome (HFRS) is a fatal disease caused by Hantaan virus (HTNV) infection. Humoral immunity is essential for effective viral clearance; however, the glycosylation characteristics of immunoglobulin G (IgG) in HFRS patients are not well known. Peripheral blood mononuclear cells from HFRS patients were obtained for B subset analysis using scRNA-seq and flow cytometry. HTNV-specific IgG antibody titers were detected by enzyme-linked immunosorbent assay, and IgG glycosylation was analyzed by ultra-performance liquid chromatography. The proportions of the antibody-secreting memory (ASM) B cells and plasmablasts (PB) were significantly expanded among acute HFRS patients. We discovered significantly increased fucosylated IgG and decreased bisecting N-acetylglucosamine during the convalescent phase of HTNV infection. Meanwhile, positive correlations were observed between ASM subsets and galactosylation/sialylation in the IgG Fc region, and between PB subsets and sialylation. Notably, the glycosylation-related genes, such as RPN1 and RPN2, were primarily expressed differentially in the ASM and PB subclusters, which were enriched in the N-glycosylation modifications of proteins through asparagine. Our findings indicated that IgG N-glycosylation may play a crucial role in combating HTNV infection and contributing to clinical recovery, which provided new insights for optimizing glycoengineered therapeutic antibodies.

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