Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Clin Exp Immunol. 2019 Aug;197(2):214-221. doi: 10.1111/cei.13302. Epub 2019 Apr 12.
A small subset of myasthenia gravis (MG) patients develop autoantibodies against muscle-specific kinase (MuSK), which are predominantly of the immunoglobulin (Ig)G4 isotype. MuSK-MG is strongly associated with HLA-DRB114, HLA-DRB116 and HLA-DQB105. In this study, the possible effects of these HLA associations on MuSK IgG autoantibody or cytokine production were investigated. Samples from 80 MG patients with MuSK antibodies were studied. The disease-associated HLA types were screened in the DNA samples. The IgG1, IgG2, IgG3 and IgG4 titres of the MuSK antibodies and the levels of interleukin (IL)-4, IL-6, IL-17A and IL-10 were measured in the sera. Comparisons were made among the groups with or without HLA-DRB114, HLA-DRB116 or HLA-DQB105. The IgG4 titres of the MuSK antibodies were higher than those of the IgG1, IgG2 and IgG3 isotypes among the whole group of patients. DRB114 (+) DRB116 (-) patients had higher levels of IgG4 antibodies than those of DRB114 (-) DRB116 (+) patients. DRB114 (+) DRB116 (+) patients also had higher levels of IgG4 antibodies than those of DRB114 (-) DRB116 (+) and DRB114 (-) DRB116 (-) patients. Higher IL-10 and lower IL-17A levels were measured in DRB114 (+) DRB116 (-) patients than in DRB114 (-) DRB116 (-) patients. The higher IgG4 titres of MuSK autoantibodies in patients carrying HLA-DRB1*14 than those in the other patients suggest a role for HLA in the production of the antibodies. The differences in IL-10 and IL-17A support the role of DRB1 in the etiopathogenesis of this autoimmune response.
一小部分重症肌无力（MG）患者会产生针对肌肉特异性激酶（MuSK）的自身抗体，这些抗体主要为 IgG4 同种型。MuSK-MG 与 HLA-DRB114、HLA-DRB116 和 HLA-DQB105 强烈相关。在这项研究中，研究了这些 HLA 关联对 MuSK IgG 自身抗体或细胞因子产生的可能影响。研究了 80 名 MuSK 抗体阳性的 MG 患者的样本。在 DNA 样本中筛选出与疾病相关的 HLA 类型。在血清中测量了 MuSK 抗体的 IgG1、IgG2、IgG3 和 IgG4 滴度以及白细胞介素（IL）-4、IL-6、IL-17A 和 IL-10 的水平。比较了 HLA-DRB114、HLA-DRB116 或 HLA-DQB105 阳性组与阴性组之间的差异。在整个患者组中，MuSK 抗体的 IgG4 滴度高于 IgG1、IgG2 和 IgG3 同种型。DRB114(+)DRB116(-)患者的 IgG4 抗体水平高于 DRB114(-)DRB116(+)患者。DRB114(+)DRB116(+)患者的 IgG4 抗体水平也高于 DRB114(-)DRB116(+)和 DRB114(-)DRB116(-)患者。与 DRB114(-)DRB116(-)患者相比，DRB114(+)DRB116(-)患者的 IL-10 水平较高，IL-17A 水平较低。与其他患者相比，携带 HLA-DRB1*14 的患者的 MuSK 自身抗体 IgG4 滴度较高，表明 HLA 在抗体产生中起作用。IL-10 和 IL-17A 的差异支持 DRB1 在这种自身免疫反应发病机制中的作用。
