Karim Md Rezaul, Zhang Hong-Yan, Yuan Jiang, Sun Qiang, Wang Yun-Fu
Department of Neurology, Taihe Hospital of Hubei University of Medicine , Shiyan , China.
Front Neurol. 2017 Feb 20;8:43. doi: 10.3389/fneur.2017.00043. eCollection 2017.
To find out if the failure in immunotolerance of myasthenia gravis (MG) is a possible aspect of deduction in Breg cells and to characterize B cell subsets in MG.
Flow cytometry detection and enzyme-linked immunosorbent assays in peripheral blood films of 10 MG patients and 10 healthy controls (HCs) were performed after isolation of B cells. The CD19CD5CD1d Breg cells percentages were measured to complement a B cell phenotype assay and frequencies of B cell subsets. The clinical outcome measures and immunological variables of patients with MG were compared with HCs.
Patients with MG had relatively lowered percentages of CD19CD5CD1d Breg cells as compared to HCs. The production of interleukin (IL)-10 and transforming growth factor (TGF)-β1 was relatively lesser in patients with MG than HCs, which were linked with more severe of MG disease status according to Myasthenia Gravis Foundation of America (MGFA) clinical classification. The reduction of cytokine production was more significant for IL-10 than TGF-β1 when compared to HCs.
It has been observed that the reduced number of B cells is able to produce IL-10 in MG patients but lesser than compared to HCs. The Bregs reduction mainly was regarded by the severity of disease status, which was highly significant and also by disease duration which was statistically significant as well. The findings of the measurement of B cell phenotype assay and frequencies of B cell subsets between MGs and HCs give us new ideas to develop B cell-mediated therapies of MG such as (1) isolated B cells of MGs could be cultured with steroids, e.g., dexamethasone to see if it induces the CD19CD5CD1d Breg cells, (2) it may observe whether induced CD19CD5CD1d Bregs have higher production of IL-10 and TGF-β1, as both are linked with disease severity, and (3) after completion steps, through further research to observe whether it improves the function of MG disease status.
探究重症肌无力(MG)免疫耐受失败是否可能是调节性B细胞(Breg细胞)减少的一个方面,并对MG中的B细胞亚群进行特征分析。
在分离出B细胞后,对10例MG患者和10名健康对照者(HCs)的外周血涂片进行流式细胞术检测和酶联免疫吸附测定。测量CD19⁺CD5⁺CD1d⁺ Breg细胞百分比以补充B细胞表型分析和B细胞亚群频率。将MG患者的临床结局指标和免疫变量与HCs进行比较。
与HCs相比,MG患者的CD19⁺CD5⁺CD1d⁺ Breg细胞百分比相对降低。MG患者白细胞介素(IL)-10和转化生长因子(TGF)-β1的产生比HCs相对较少,根据美国重症肌无力基金会(MGFA)临床分类,这与更严重的MG疾病状态相关。与HCs相比,IL-10的细胞因子产生减少比TGF-β1更显著。
据观察,MG患者中能够产生IL-10的B细胞数量减少,但比HCs少。Bregs减少主要与疾病状态严重程度密切相关(具有高度显著性),也与病程相关(具有统计学显著性)。MG患者与HCs之间B细胞表型分析和B细胞亚群频率测量的结果为开发MG的B细胞介导疗法提供了新思路,例如:(1)MG患者分离出的B细胞可以用类固醇如地塞米松培养,观察是否诱导产生CD19⁺CD5⁺CD1d⁺ Breg细胞;(2)观察诱导产生的CD19⁺CD5⁺CD1d⁺ Bregs是否具有更高的IL-10和TGF-β1产生,因为两者都与疾病严重程度相关;(3)完成上述步骤后,通过进一步研究观察是否改善MG疾病状态的功能。