Relation of HLA-DRB1 to IgG4 autoantibody and cytokine production in muscle-specific tyrosine kinase myasthenia gravis (MuSK-MG)

Çebi M., Durmuş H., YILMAZ V., Yentür S., Aysal F., Oflazer P., ...More

Clinical and Experimental Immunology, vol.197, no.2, pp.214-221, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 197 Issue: 2
  • Publication Date: 2019
  • Doi Number: 10.1111/cei.13302
  • Journal Name: Clinical and Experimental Immunology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.214-221
  • Keywords: IgG isotype, HLA, MuSK, myasthenia gravis
  • Istanbul Medipol University Affiliated: No


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-DRB1*14, HLA-DRB1*16 and HLA-DQB1*05. 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-DRB1*14, HLA-DRB1*16 or HLA-DQB1*05. The IgG4 titres of the MuSK antibodies were higher than those of the IgG1, IgG2 and IgG3 isotypes among the whole group of patients. DRB1*14 (+) DRB1*16 (–) patients had higher levels of IgG4 antibodies than those of DRB1*14 (–) DRB1*16 (+) patients. DRB1*14 (+) DRB1*16 (+) patients also had higher levels of IgG4 antibodies than those of DRB1*14 (–) DRB1*16 (+) and DRB1*14 (–) DRB1*16 (–) patients. Higher IL-10 and lower IL-17A levels were measured in DRB1*14 (+) DRB1*16 (–) patients than in DRB1*14 (–) DRB1*16 (–) 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.