Relation ofHLA-DRB1to IgG4 autoantibody and cytokine production in muscle-specific tyrosine kinase myasthenia gravis (MuSK-MG)

Abstract

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.

Common Denominators in the Immunobiology of IgG4 Autoimmune Diseases: What Do Glomerulonephritis, Pemphigus Vulgaris, Myasthenia Gravis, Thrombotic Thrombocytopenic Purpura and Autoimmune Encephalitis Have in Common?

“…The higher IgG4 titers 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 (124).…”

“…There are contradictory observations. Supporting evidence: 1) MuSK MG patients with the HLA-DRB1*14 type had elevated antibody titers and higher levels of IL-17A and IL-10 than MuSK MG patients with different haplotype (124). The higher IgG4 titers 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.…”

Clinical and Prognostic Value of Immunogenetic Characteristics in Anti-LGI1 Encephalitis

“… 31 Conversely, we demonstrated herein that CSF positivity and IgG isotypes did not significantly differ according to DRB1*07:01 carrier status in LGI1-Abs LE. Nevertheless, other immune effectors such as cytokines may vary depending on the HLA involved, 32 explaining the differential clinical presentation. However, larger cohorts are necessary to further investigate the differential characteristics of patients according to their HLA.…”

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG)

“…Furthermore, autoantibodies in LGI1-encephalitis are usually of the IgG4 subclass – an observation made in several autoimmunopathies, 57 many of which have a genetic predisposition. 58 , 59 However, this genetic predisposition is not different between genders. 56 …”