In‐depth peripheral CD4+ T profile correlates with myasthenic crisis
Abstract Objective Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in‐hospital mortality. We aimed to identify immune signatures using in‐depth profiling in MC, and to as...
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doaj-e13da6b026764a6caf043050bd084c0b2021-08-09T12:00:31ZengWileyAnnals of Clinical and Translational Neurology2328-95032021-04-018474976210.1002/acn3.51312In‐depth peripheral CD4+ T profile correlates with myasthenic crisisXiao Huan0Sushan Luo1Huahua Zhong2Xueying Zheng3Jie Song4Lei Zhou5Jun Lu6Ying Wang7Yafang Xu8Jianying Xi9Zhangyu Zou10Sheng Chen11Chongbo Zhao12Department of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Biostatistics School of Public Health and Key Laboratory of Public Health Safety Fudan University Shanghai ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Pharmacy Huashan Hospital Fudan University Shanghai ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaDepartment of Neurology Institute of Clinical Neurology Fujian Medical University Union HospitalFujian Medical University Fuzhou ChinaDepartment of Neurology Institute of Clinical Neurology Fujian Medical University Union HospitalFujian Medical University Fuzhou ChinaDepartment of Neurology Huashan Hospital Fudan University Shanghai ChinaAbstract Objective Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in‐hospital mortality. We aimed to identify immune signatures using in‐depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally. Methods We studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow‐up visits occurred prospectively from crisis to 6 months off‐mechanical ventilation. The frequencies of 20 CD4+ T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis. Results Patients in crisis exhibited a proinflammatory CD4+T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P < 0.001), Tnaive in Tfh cells (P < 0.001), ICOS−Tfh cells (P = 0.017), and T central memory in Tfh (P = 0.022) compared with controls, and increased frequencies of Tregs (P = 0.026) and Tfh17 (P = 0.045) compared with non‐crisis MG. Cytokine cascade was identified in crisis including the ones associated with Th1 (IL‐1β/2/12p70/18/27/IFN‐γ/TNF‐α), Th2 (IL‐4/5/13), Th17 (IL‐6/17A/21/22/23/GM‐CSF), Th9 (IL‐9), and Treg (IL‐10). Longitudinally, seven immune biomarkers including Tregs, IL‐2/4/17A/IFN‐γ/TNF‐α/GM‐CSF had significant correlations with MG‐activities of daily living score. Interpretation Vigorous inflammatory CD4+ T signatures were identified in MC and are associated with clinical severity. Future research is needed to explore its potential candidacy for therapeutic intervention and predicting impending crisis.https://doi.org/10.1002/acn3.51312 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiao Huan Sushan Luo Huahua Zhong Xueying Zheng Jie Song Lei Zhou Jun Lu Ying Wang Yafang Xu Jianying Xi Zhangyu Zou Sheng Chen Chongbo Zhao |
spellingShingle |
Xiao Huan Sushan Luo Huahua Zhong Xueying Zheng Jie Song Lei Zhou Jun Lu Ying Wang Yafang Xu Jianying Xi Zhangyu Zou Sheng Chen Chongbo Zhao In‐depth peripheral CD4+ T profile correlates with myasthenic crisis Annals of Clinical and Translational Neurology |
author_facet |
Xiao Huan Sushan Luo Huahua Zhong Xueying Zheng Jie Song Lei Zhou Jun Lu Ying Wang Yafang Xu Jianying Xi Zhangyu Zou Sheng Chen Chongbo Zhao |
author_sort |
Xiao Huan |
title |
In‐depth peripheral CD4+ T profile correlates with myasthenic crisis |
title_short |
In‐depth peripheral CD4+ T profile correlates with myasthenic crisis |
title_full |
In‐depth peripheral CD4+ T profile correlates with myasthenic crisis |
title_fullStr |
In‐depth peripheral CD4+ T profile correlates with myasthenic crisis |
title_full_unstemmed |
In‐depth peripheral CD4+ T profile correlates with myasthenic crisis |
title_sort |
in‐depth peripheral cd4+ t profile correlates with myasthenic crisis |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2021-04-01 |
description |
Abstract Objective Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in‐hospital mortality. We aimed to identify immune signatures using in‐depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally. Methods We studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow‐up visits occurred prospectively from crisis to 6 months off‐mechanical ventilation. The frequencies of 20 CD4+ T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis. Results Patients in crisis exhibited a proinflammatory CD4+T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P < 0.001), Tnaive in Tfh cells (P < 0.001), ICOS−Tfh cells (P = 0.017), and T central memory in Tfh (P = 0.022) compared with controls, and increased frequencies of Tregs (P = 0.026) and Tfh17 (P = 0.045) compared with non‐crisis MG. Cytokine cascade was identified in crisis including the ones associated with Th1 (IL‐1β/2/12p70/18/27/IFN‐γ/TNF‐α), Th2 (IL‐4/5/13), Th17 (IL‐6/17A/21/22/23/GM‐CSF), Th9 (IL‐9), and Treg (IL‐10). Longitudinally, seven immune biomarkers including Tregs, IL‐2/4/17A/IFN‐γ/TNF‐α/GM‐CSF had significant correlations with MG‐activities of daily living score. Interpretation Vigorous inflammatory CD4+ T signatures were identified in MC and are associated with clinical severity. Future research is needed to explore its potential candidacy for therapeutic intervention and predicting impending crisis. |
url |
https://doi.org/10.1002/acn3.51312 |
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