重症肌无力患者外周血中IL-21的表达 及其与血清抗AChR抗体类别转换的关系

目的：探讨白细胞介素(IL)-21在重症肌无力(MG)发病中的作用及其对血清抗乙酰胆碱受体(AChR)抗体类别转换的影响。方法：采集26例MG患者和18例健康对照者的外周血，应用ELISA技术检测外周血血清中抗AChR-IgG及其亚型IgG1，IgG2，IgG3的水平以及IL-21的浓度，利用RT-PCR技术检测外周血单个核细胞上IL-21R mRNA的表达水平，采用流式细胞学技术检测其中8例患者B细胞上IL-21R的表达水平，并分析它们之间的关系。结果：MG患者组血清中IL-21浓度（31.686±8.499 pg/mL）高于正常对照组（15.147±6.366 pg/mL），差异具有统计学意义（P＜0.01）；MG患者组 PBMCs上IL-21R mRNA的表达（0.139±0.052）高于正常对照组(0.101±0.022)，差异具有统计学意义（P＜0.05）；但二者在眼肌型和全身型亚组中差异均无统计学意义（P＞0.05）。8例MG患者B细胞上的IL-21R的表达水平(1.074±0.375)高于正常对照组(0.389±0.391)，差异具有统计学意义（P＜0.05）。抗AChR-Ab阳性患者血清IL-21浓度与抗AChR-IgG水平呈正相关，相关系数为0.689（P＜0.05），但其与IgG1，IgG2，IgG3亚型的水平均无相关性（P＞0.05）；PBMCs上IL-21R mRNA的表达与血清抗AChR-IgG及其IgG1，IgG2，IgG3亚型的水平均无相关性（P＞0.05）；B细胞上IL-21R的表达与抗AChR-IgG及IgG1，IgG3亚型水平呈正相关（分别为P＜0.05，P＜0.01，P＜0.05），而与抗AChR-IgG2的水平无相关性（P＞0.05）。结论：IL-21可能通过作用于B细胞上的IL-21R，影响MG患者血清中抗AChR抗体向IgG1和IgG3亚型转换，从而对MG发病起促进作用。

Expression of IL 21 in the peripheral blood of myasthenia gravis patients and its correlation with anti AChR Ab class switch

ObjectiveTo explore the role of IL-21 in the pathogenesis of myasthenia gravis (MG) and its influence on the the class switch of anti-AChR antibodies. MethodsBlood was taken from 26 patients and 18 healthy controls, and the expression of IL-21R mRNA in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR. The expression of IL-21R on B lymphocytes was measured by flow cytometry, while the concentrations of serum IL-21 and the levels of anti-AChR-IgG and its isotype IgG1, IgG2, and IgG3 were tested by ELISA. ResultsThe serum concentration of IL-21 in the MG group was higher than that in the control group (31.686±8.499 pg/mL, 15.147±6.366 pg/mL) and the difference was significant (P＜0.01). IL-21R mRNA expressed on PBMCs in the MG group was higher than that in the control group (0.139±0.052, 0.101±0.022), and the difference was significant (P＜0.05). There was no difference between ocular MG and generalized MG subgroup (P＞0.05). Compared with the control group, the expression of IL-21R on B lymphocytes also increased in the MG group (P＜0.05). In the anti-AChR-Ab positive MG group, the serum concentration of IL-21 showed positive correlation with anti-AChR-IgG(P＜0.05),but no correlation with its isotype IgG1, IgG2, and IgG3, respectively(P＞0.05). Expression of IL-21R mRNA in the PBMCs showed no correlation with the level of serum anti-AChR-IgG and its isotype IgG1, IgG2, and IgG3, respectively(P＞0.05); however the expression of IL-21R in B lymphocytes showed positive correlation with anti-AChR-IgG and it’s isotype IgG1 and IgG3 (P＜0.05，P＜0.01，P＜0.05), but no correlation with IgG2 (P＞0.05). ConclusionIL-21 might induce the class switch of anti-AChR antibodies to IgG1 and IgG3 isotype through IL-21R on B lymphocytes which promotes the pathogenesis of the MG.