Hu Bo, Tian Xiaolin, Huang Huifen, Jian Ai, Ouyang Song, Yin Weifan, Duan Weiwei, Yang Huan
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010 Sep;35(9):958-63. doi: 10.3969/j.issn.1672-7347.2010.09.010.
To 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.
Blood 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 IgG(1), IgG(2), and IgG(3) were tested by ELISA.
The 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 IgG(1), IgG(2), and IgG(3), 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 IgG(1), IgG(2), and IgG(3), respectively(P>0.05); however the expression of IL-21R in B lymphocytes showed positive correlation with anti-AChR-IgG and it's isotype IgG(1) and IgG(3) (P<0.05,P<0.01,P<0.05), but no correlation with IgG(2) (P>0.05).
IL-21 might induce the class switch of anti-AChR antibodies to IgG(1) and IgG(3) isotype through IL-21R on B lymphocytes which promotes the pathogenesis of the MG.
探讨白细胞介素-21(IL-21)在重症肌无力(MG)发病机制中的作用及其对抗乙酰胆碱受体(AChR)抗体类别转换的影响。
采集26例MG患者及18名健康对照者的血液,采用逆转录聚合酶链反应(RT-PCR)检测外周血单个核细胞(PBMCs)中IL-21受体(IL-21R)mRNA的表达。采用流式细胞术检测B淋巴细胞上IL-21R的表达,同时采用酶联免疫吸附测定(ELISA)检测血清IL-21浓度、抗AChR-IgG及其IgG1、IgG2和IgG3亚型的水平。
MG组血清IL-21浓度高于对照组(31.686±8.499 pg/mL,15.147±6.366 pg/mL),差异有统计学意义(P<0.01)。MG组PBMCs上IL-21R mRNA的表达高于对照组(0.139±0.052,0.101±0.022),差异有统计学意义(P<0.05)。眼肌型MG和全身型MG亚组之间无差异(P>0.05)。与对照组相比,MG组B淋巴细胞上IL-21R的表达也增加(P<0.05)。在抗AChR抗体阳性的MG组中,血清IL-21浓度与抗AChR-IgG呈正相关(P<0.05),但与IgG1、IgG2和IgG3亚型分别无相关性(P>0.05)。PBMCs中IL-21R mRNA的表达与血清抗AChR-IgG及其IgG1、IgG2和IgG3亚型的水平分别无相关性(P>0.05);然而,B淋巴细胞上IL-21R的表达与抗AChR-IgG及其IgG1和IgG3亚型呈正相关(P<0.05,P<0.01,P<0.05),但与IgG2无相关性(P>0.05)。
IL-21可能通过B淋巴细胞上的IL-21R诱导抗AChR抗体向IgG1和IgG3亚型的类别转换,从而促进MG的发病机制。