In-depth peripheral CD4(+) T profile correlates with myasthenic crisis.
In-depth peripheral CD4(+) T profile correlates with myasthenic crisis.
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深入的外周 CD4( ) T 谱与肌无力危象相关
DOI：
10.1002/acn3.51312
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发表时间：
2021-04
影响因子：
5.3
通讯作者：
Zhao C
中科院分区：
文献类型：
--
作者：
Huan X;Luo S;Zhong H;Zheng X;Song J;Zhou L;Lu J;Wang Y;Xu Y;Xi J;Zou Z;Chen S;Zhao C
重症肌无力（MG）是一种由抗神经肌肉接头自身抗体引起的自身免疫性疾病。肌无力危象（MC）是MG最严重的状态，住院死亡率高。我们的目的是在MC中使用深入分析来识别免疫特征，并纵向评估免疫生物标志物与临床严重程度之间的相关性。我们研究了181名参与者，包括57名健康对照者，96名从未经历过危机的MG患者和28名MC患者，从2018年12月到2020年6月。前瞻性随访访视从危象到无机械通气6个月。采用相关分析和主成分分析法对20种CD 4 + T细胞亚群和18种细胞因子的频率与临床评分进行相关性分析。危象患者表现出促炎性CD 4 +T细胞反应，Th 1细胞升高，（P = 0.026），Th 17细胞（P = 0.032）;滤泡辅助性T细胞2（Tfh 2）减少（P < 0.001），Tfh细胞的Tnaive（P < 0.001），ICOS−Tfh细胞与对照组相比，Tfh（P = 0.017）和T中枢记忆（P = 0.022），与非危象MG相比，Tfh（P = 0.026）和Tfh 17（P = 0.045）的频率增加。在危象中发现了细胞因子级联反应，包括与Th 1（IL-1β/2/12 p70/18/27/IFN-γ/TNF-α）、Th 2（IL-4/5/13）、Th 17（IL-6/17 A/21/22/23/GM-CSF）、Th 9（IL-9）和Treg（IL-10）相关的细胞因子级联反应。纵向上，七种免疫生物标志物（包括T细胞因子、IL-2/4/17 A/IFN-γ/TNF-α/GM-CSF）与MG-日常生活活动评分显著相关。在MC中发现了强烈的炎性CD 4 + T标记，并与临床严重程度相关。未来的研究需要探索其潜在的候选人治疗干预和预测即将发生的危机。
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. 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. 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. 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.
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