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

作者全名："Fan, Rui; Que, Wenjun; Liu, Zhuoting; Zheng, Wei; Guo, Xia; Liu, Linqi; Xiao, Fei"

作者地址："[Fan, Rui; Que, Wenjun; Liu, Zhuoting; Zheng, Wei; Guo, Xia; Liu, Linqi; Xiao, Fei] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Que, Wenjun] Chongqing Med Univ, Dept Blood Transfus, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Guo, Xia] Zunyi Med Univ, Dept Neurol, Affiliated Hosp 2, Intersect Xinlong Ave & Xinpu Ave New Pu Dist, Zunyi 563000, Peoples R China; [Xiao, Fei] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, 1st Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Xiao, F (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, 1st Youyi Rd, Chongqing 400016, Peoples R China."

来源：CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000897839100008

JCR分区：Q1

影响因子：8.6

年份：2022

卷号：245

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Myasthenia gravis; Cohort; Immune; monocyte; NK cell; Mass cytometry; Immune check point

摘要："The pathogenesis and progression of myasthenia gravis (MG), an autoimmune disease, involve abnormal func-tion 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+ naive 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."

基金机构："Future Medical Youth Innovation Team Program of Chongqing Medical University; Fifth Senior Medical Talents Program of Chongqing for Young and Middle-aged, Middle-aged Medical Excellence Team Program of Chongqing; Chongqing chief expert studio project, China; [W0043]"

基金资助正文："Funding This work was supported by Future Medical Youth Innovation Team Program of Chongqing Medical University (No. W0043) , the Fifth Senior Medical Talents Program of Chongqing for Young and Middle-aged, Middle-aged Medical Excellence Team Program of Chongqing, and Chongqing chief expert studio project, China."