PMID- 30929252
OWN - NLM
STAT- MEDLINE
DCOM- 20200421
LR  - 20200801
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 197
IP  - 2
DP  - 2019 Aug
TI  - Relation of HLA-DRB1 to IgG4 autoantibody and cytokine production in 
      muscle-specific tyrosine kinase myasthenia gravis (MuSK-MG).
PG  - 214-221
LID - 10.1111/cei.13302 [doi]
AB  - 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.
CI  - (c) 2019 British Society for Immunology.
FAU - Cebi, M
AU  - Cebi M
AD  - Department of Physiology, Istanbul Medical Faculty, Istanbul University, 
      Istanbul, Turkey.
FAU - Durmus, H
AU  - Durmus H
AD  - Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, 
      Turkey.
FAU - Yilmaz, V
AU  - Yilmaz V
AD  - Department of Physiology, Istanbul Medical Faculty, Istanbul University, 
      Istanbul, Turkey.
FAU - Yentur, S P
AU  - Yentur SP
AD  - Department of Physiology, Istanbul Medical Faculty, Istanbul University, 
      Istanbul, Turkey.
FAU - Aysal, F
AU  - Aysal F
AD  - Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatric 
      and Neurological Diseases, Istanbul, Turkey.
AD  - Department of Neurology, Istanbul Medipol University School of Medicine, 
      Istanbul, Turkey.
FAU - Oflazer, P
AU  - Oflazer P
AD  - Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, 
      Turkey.
FAU - Parman, Y
AU  - Parman Y
AD  - Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, 
      Turkey.
FAU - Deymeer, F
AU  - Deymeer F
AD  - Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, 
      Turkey.
FAU - Saruhan-Direskeneli, G
AU  - Saruhan-Direskeneli G
AUID- ORCID: 0000-0002-6903-7173
AD  - Department of Physiology, Istanbul Medical Faculty, Istanbul University, 
      Istanbul, Turkey.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190412
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (IL10 protein, human)
RN  - 0 (IL17A protein, human)
RN  - 0 (IL4 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Cholinergic)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Autoantibodies/blood/*immunology
MH  - Autoimmunity/immunology
MH  - Child
MH  - Female
MH  - HLA-DRB1 Chains/*immunology
MH  - Humans
MH  - Immunoglobulin G/*immunology
MH  - Interleukin-10/blood
MH  - Interleukin-17/blood
MH  - Interleukin-4/blood
MH  - Interleukin-6/blood
MH  - Male
MH  - Middle Aged
MH  - Myasthenia Gravis/genetics/*immunology
MH  - Receptor Protein-Tyrosine Kinases/genetics/*immunology
MH  - Receptors, Cholinergic/genetics/*immunology
MH  - Young Adult
PMC - PMC6642874
OTO - NOTNLM
OT  - HLA
OT  - IgG isotype
OT  - MuSK
OT  - myasthenia gravis
COIS- The authors declare no conflicts of interest.
EDAT- 2019/04/01 06:00
MHDA- 2020/04/22 06:00
PMCR- 2020/08/01
CRDT- 2019/04/01 06:00
PHST- 2019/03/27 00:00 [accepted]
PHST- 2019/04/01 06:00 [pubmed]
PHST- 2020/04/22 06:00 [medline]
PHST- 2019/04/01 06:00 [entrez]
PHST- 2020/08/01 00:00 [pmc-release]
AID - CEI13302 [pii]
AID - 10.1111/cei.13302 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2019 Aug;197(2):214-221. doi: 10.1111/cei.13302. Epub 2019 Apr 
      12.