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

Haemorrhagic fever with renal syndrome (HFRS) is a fatal disease caused by Hantaan virus (HTNV) infection. Humoral immunity is essential for effective viral clearance, but the glycosylation characteristics of immunoglobulin G (IgG) in HFRS patients is 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. However, 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 were primarily differentially expressed in the ASM and PB subclusters, such as PRN1 and PRN2 , 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.