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

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 author has email address
Haifeng Hou author has email address

Key Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, China
The Second Affiliated Hospital of Shandong First Medical University, Taian, China
School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, China
Medical Records and Statistics Management Office, Tengzhou Central People’s Hospital, Zaozhuang, China
Department of Neurobiology and Physiology, School of Clinical and Basic Medicine, Shandong First Medical University& Shandong Academy of Medical Sciences, Ji’nan, China
Baoji Central Hospital, Baoji, China
School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China
National Virus Reference Laboratory, School of Medicine, University College Dublin, Dublin, Ireland
International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Institute of Virology, Shanghai Jiao Tong University School of Medicine, Shanghai, China

https://doi.org/10.7554/eLife.106989.1

Open access
Copyright information

Figures and data

The flow chart of HFRS patient recruitment in Baoji Central Hospital in Shaanxi province from November 2019 to January 2022.

Immunophenotypic remodeling in the B-cell subsets during acute HFRS.
(A) t-distributed stochastic neighbor embedding (t-SNE) plot showing antibody secreting memory B cells (ASM), double negative (DN) B cells, intermediate memory cells (IM), marginal zone-like cells (MZB), naïve B cells, plasmablasts (PB), quiescent resting memory cells (RM), and exhausted tissue-like memory B cells (TLM) of PBMCs identified using an integrated and classification analysis. (B) t-SNE projection of canonical markers, including CD19, CD27, CD38, IgD, and IgM. (C) Proportions of the eight B cell subsets, colored by the healthy group (green) and HTNV groups (red). Boxplot features: minimum box, 25th percentile; center, median; maximum box, 75th percentile. (D) Frequency of the eight B cell subsets in between the healthy group (n = 8) and HTNV groups (n = 15). (E) FACS gating strategy for the measurement of the B-cell subsets: activated memory B cells (CD21^- CD27⁺, AM), RM B cells (CD21⁺ CD27⁺), IM B cells (CD21⁺ CD27^-), TLM B cells (CD21^- CD27^-), naive B cells (CD27^- IgD⁺), MZB B cells (CD27⁺ IgD⁺), ASM B cells (CD27⁺ IgD^-), DN B cells (CD27^- IgD^-), PB (CD38⁺ CD27⁺), and class-switched memory B cells (CD38^- CD27⁺, CSM), respectively. (F) The proportion of ASM, CSM, naive B, and PB cells in CD19⁺ B cells in the acute and convalescent HFRS patients. Data are presented as mean ± SEM in panels C and F. *p<0.05 (Student’s t-test).

Glycosylation modification of antibodies associated with HTNV infection.
(A) Changes of different glycosylation types in both HTNV-NP specific IgG negative and positive plasma from 24 HFRS patients. (B) Differential IgG glycosylation patterns across antibody titer levels quantified by ELISA. (C) Comparison of different glycosylation levels before and after the fourfold increase in the IgG antibody titers. *p<0.05, **p<0.01, ***p<0.001. For paired samples, Wilcoxon Signed Rank Test was used to assess the difference.

Glycosylation modifications of antibodies primarily deprived from antibody-secreting and plasmablast subpopulations.
(A) The correlation between the proportion of PB cells and the sialylation level. (B) The correlation between the proportion of ASM cells and the sialylation level. (C) The correlation between the proportion of ASM cells and the galactosylation level. (D) Dot plot shows the expression levels of glycosylation-related genes in the eight B cell groups. The pink color represents mannose related genes, the green color represents N-glycosylation related genes, the orange color represents galactosylation related genes, the purple represents sialylation related genes, and the red color represents fucosylation related genes. (E) Enriched pathways in the plasmablast and ASM subsets by GO enrichment analysis of the DEGs. (F) The GSEA map presents the enrichment score of GRGs in N-Glycan biosynthesis.

Single-cell transcriptomes of PBMCs from patients with HFRS.
(A) Uniform manifold approximation and projection (UMAP) presentation of the major peripheral immune cell types in the PBMCs from 15 HFRS patients and 8 healthy controls. (B) Dot plot shows the expression levels of canonical marker-related genes in the different subpopulations. (C) UMAP presentation of the major peripheral immune cell types among HFRS and healthy control groups. (D) Proportions of the eight cell subsets, colored by the healthy group (green) and HTNV groups (red). Boxplot features: minimum box, 25th percentile; center, median; maximum box, 75th percentile. (E) Frequency of the eight cell subsets in between the healthy group (n = 8) and the HTNV group (n = 15). (F) The UMAP plot shows the differentiation trajectories of different cell types calculated by pseudotime analysis.

Dynamic analysis of the B-cell subsets in HFRS patients.
(A) Expression of MZB in CD19⁺ B cells. (B) Expression of DN in CD19⁺ B cells. (C) Expression of TLM in CD19⁺ B cells. (D) Expression of AM in CD19⁺ B cells. (E) Expression of RM in CD19⁺ B cells. (F) Expression of IM in CD19⁺ B cells.

The differentially expressed genes and their functional changes in the B cell subsets post HTNV infection.
(A) The volcano plot shows the differentially expressed genes of different B cell subsets in acute HFRS patients. The red font represents the upregulation of the B cell subpopulations, and the blue font represents the downregulation of the B cell subpopulations. (B and C) The volcano plot displays the differentially expressed genes in upregulation B cell subpopulations including antibody secreting memory B cells, plasmablasts, and quiescent resting memory B cells (B), and downregulation B cell subpopulations including naive B cells, double negative B cells, and intermediate memory B cells (C).

Sign up for email alerts