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

• Published in: Clinical and experimental immunology Vol. 197; no. 2; pp. 214 - 221
• Main Authors: Çebi, M., Durmuş, H., Yılmaz, V., Yentür, S.P., Aysal, F., Oflazer, P., Parman, Y., Deymeer, F., Saruhan‐Direskeneli, G.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2019; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Aged; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Autoimmunity - immunology; Child; Cytokines; Deoxyribonucleic acid; DNA; Drb1 protein; Female; Histocompatibility antigen HLA; HLA; HLA-DRB1 Chains - immunology; Humans; IgG isotype; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulins; Interleukin-10 - blood; Interleukin-17 - blood; Interleukin-4 - blood; Interleukin-6 - blood; Isotypes; Male; Middle Aged; Muscles; MuSK; Myasthenia; Myasthenia gravis; Myasthenia Gravis - genetics; Myasthenia Gravis - immunology; Neuromuscular junctions; Original; Protein-tyrosine kinase; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - immunology; Receptors, Cholinergic - genetics; Receptors, Cholinergic - immunology; Young Adult; myasthenia gravis; IgG isotype; MuSK; HLA
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13302

Summary 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. The possible effects of MuSK‐MG associated HLA‐DRB1*14, HLA‐DRB1*16 and HLA‐DQB1*05 on MuSK IgG autoantibody or cytokine production were investigated. The IgG4 titres of the MuSK antibodies were higher than those of the IgG1, IgG2 and IgG3 isotypes. DRB1*14 (+) DRB1*16 (–) and DRB1*14 (+) DRB1*16 (+) patients had higher levels of IgG4 antibodies than those of DRB1*14 (–) DRB1*16 (+). The higher IgG4 titres in patients carrying HLA‐DRB1*14 suggest a role for HLA‐DRB1 in the production of the antibodies in the etiopathogenesis of this autoimmune response.