Single-cell mapping reveals dysregulation of immune cell populations and VISTA+ monocytes in myasthenia gravis

Rui Fan; Wenjun Que; Zhuoting Liu; Wei Zheng; Xia Guo; Linqi Liu; Fei Xiao

doi:10.1016/j.clim.2022.109184

Single-cell mapping reveals dysregulation of immune cell populations and VISTA+ monocytes in myasthenia gravis

Clin Immunol. 2022 Dec:245:109184. doi: 10.1016/j.clim.2022.109184. Epub 2022 Nov 11.

Authors

Rui Fan¹, Wenjun Que², Zhuoting Liu¹, Wei Zheng¹, Xia Guo³, Linqi Liu¹, Fei Xiao⁴

Affiliations

¹ Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
² Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China; Department of Blood Transfusion, the First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing 400016, China.
³ Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China; Department of Neurology, the Second Affiliated Hospital of Zunyi Medical University, The Intersection of Xinlong Avenue and Xinpu Avenue in New Pu District, Zunyi 563000, China.
⁴ Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China. Electronic address: feixiao81@126.com.

PMID: 36372318
DOI: 10.1016/j.clim.2022.109184

Abstract

The pathogenesis and progression of myasthenia gravis (MG), an autoimmune disease, involve abnormal function and composition of several immune cell populations. However, details of this dysregulation remain unclear. We performed a cross-section analysis using cytometry time-of-flight on blood samples from 12 generalized MG without glucocorticoid or other immunosuppressant treatment, and 10 sex- and age-matched healthy controls. Combining data from an external validation cohort (MG n = 38, control n = 21), bulk-RNA sequencing and single-cell RNA sequencing, alterations in immune cell populations and differential expression of immune check point were revealed. Several switched memory B cell subsets (CD3- CD19+ CD27+ IgD- CD38+/-) were increased in MG patients. The number of HLA- DQ- CD38+ naïve B cells was higher in MG patients and correlated with the quantitative MG score (QMG). Among NK cells, the number of CD56+ CD16+ NK cells and CD56+ CD16+ CD8+ NK cells were decreased in MG patients and positively correlated with QMG. VISTA+ monocytes were increased in MG patients. Classical T cell subsets showed no significant change; however, the expression of VISTA, LAG3, CTLA4, and CXCR5 was higher in T cells from MG patients. The expression of CD38 was higher in neutrophils from MG patients. The external validation cohort validated the dysregulation of NK cell subtypes, and differences were also observed in subgroups of patients. Bulk-RNA sequencing also revealed increased mRNA expression of VSIR in monocytes of MG patients compared to those from healthy controls, and the antigen presentation and processing pathway was identified as enriched in the functional characterization of VISTA+ monocytes via single-cell RNA sequencing. Our study revealed alterations in several immune cell subsets and identified potential cellular biomarkers for MG diagnosis and disease severity assessment. In addition, the abnormal expression of multiple immune checkpoints in MG provides further rationale for the investigation of immune-checkpoint-related therapy.

Keywords: Cohort; Immune; Immune check point; Mass cytometry; Myasthenia gravis; NK cell; monocyte.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Flow Cytometry
Humans
Killer Cells, Natural
Monocytes*
Myasthenia Gravis* / metabolism
T-Lymphocyte Subsets