From the Department of Neurology (S.A., C.F., T.M.), Graduate School of Medical Science, Kyoto Prefectural University of Medicine; Department of Geriatric Medicine and Neurology (H.O.), Ehime University Graduate School of Medicine, Toon; Department of Neurology (M.H., R.T.), Kyoto University Graduate School of Medicine; Department of Neurology (M.H., Y.O., Y.H., T.K.), Kansai Medical University Medical Center, Osaka, Japan; Brigham and Women's Hospital (K. Kimura), Harvard Medical School, Boston, MA; Department of Neurology (K. Kawamura), National Hospital Organization Minami Kyoto Hospital; and Department of Immunology (H.U.), Kyoto University Graduate School of Medicine, Japan.
Neurol Neuroimmunol Neuroinflamm. 2021 Jan 12;8(2). doi: 10.1212/NXI.0000000000000945. Print 2021 Mar.
To clarify functional alterations of follicular helper T cells (Tfh) in myasthenia gravis (MG) because Tfh play important roles in helping B cells generate antibody-producing cells.
A total of 24 immunotherapy-naive patients with anti-acetylcholine receptor (AchR) antibody-positive MG and 18 age-matched healthy subjects (HS) were enrolled. Samples from 6 patients were available for posttreatment analysis. Subsets of circulating Tfh (cTfh) and B cells were identified by flow cytometry analysis of surface molecules. Cytokine production by isolated cTfh subsets from 5 patients with MG and 5 HS was measured in vitro. Analysis was performed to examine the correlation between the frequency of cTfh subsets and that of plasmablasts and between cTfh subsets and the quantitative MG score.
cTfh increased with elevated expression of inducible T-cell costimulator (ICOS) in patients with MG. cTfh shifted to Th2 and Th17 over Th1 in MG. ICOScTfh produced significantly higher levels of interleukin (IL)-21, IL-4, and IL-17A than ICOS cTfh only in patients with MG. The frequency of cTfh within CD4 T cells was more closely associated with disease severity than the serum anti-AchR antibody titer and frequency of plasmablasts within B cells. Abnormalities of cTfh were improved after immunotherapy in parallel with clinical improvement.
Alternation of cTfh is a key feature in the development of MG and may become a biomarker for disease severity and therapeutic efficacy.
This study provides Class II evidence that the level of cTfh is associated with disease severity in patients with MG.
阐明重症肌无力（MG）患者滤泡辅助 T 细胞（Tfh）的功能改变，因为 Tfh 在帮助 B 细胞产生产生抗体的细胞中发挥重要作用。
共纳入 24 例抗乙酰胆碱受体（AchR）抗体阳性的免疫治疗初治 MG 患者和 18 名年龄匹配的健康对照者（HS）。6 例患者的样本可用于治疗后分析。通过流式细胞术分析表面分子鉴定循环 Tfh（cTfh）和 B 细胞亚群。体外测量 5 例 MG 患者和 5 例 HS 患者分离的 cTfh 亚群产生的细胞因子。分析 cTfh 亚群的频率与浆母细胞的频率以及 cTfh 亚群与定量 MG 评分之间的相关性。
MG 患者 cTfh 随着诱导型 T 细胞共刺激因子（ICOS）的表达增加而增加。MG 患者 cTfh 向 Th2 和 Th17 偏移，而 Th1 减少。仅在 MG 患者中，ICOScTfh 产生的白细胞介素（IL）-21、IL-4 和 IL-17A 水平明显高于 ICOS cTfh。CD4 T 细胞内 cTfh 的频率与疾病严重程度的相关性比血清抗 AchR 抗体滴度和 B 细胞内浆母细胞的频率更密切。免疫治疗后，cTfh 的异常与临床改善平行改善。
cTfh 的改变是 MG 发展的一个关键特征，可能成为疾病严重程度和治疗效果的生物标志物。
本研究提供了 II 级证据，表明 cTfh 水平与 MG 患者的疾病严重程度相关。
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