PMID- 26493475
OWN - NLM
STAT- MEDLINE
DCOM- 20160927
LR  - 20151221
IS  - 1879-0542 (Electronic)
IS  - 0165-2478 (Linking)
VI  - 168
IP  - 2
DP  - 2015 Dec
TI  - Ocular myasthenia gravis induced by human acetylcholine receptor ϵ subunit 
      immunization in HLA DR3 transgenic mice.
PG  - 306-12
LID - S0165-2478(15)30050-X [pii]
LID - 10.1016/j.imlet.2015.10.009 [doi]
AB  - Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) 
      and acetylcholine receptor (AChR) antibody positive MG patients may occasionally 
      present with isolated ocular symptoms. Although experimental autoimmune 
      myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics 
      clinical and immunopathological aspects of MG, EOM are usually not affected. We 
      have previously developed an EAMG model, which imitates EOM symptoms of MG by 
      immunization of human leukocyte antigen (HLA) transgenic mice with alpha or 
      gamma-subunits of human AChR (H-AChR). To investigate the significance of the 
      ϵ-subunit in ocular MG, we immunized HLA-DR3 and HLA-DQ8 transgenic mice with 
      recombinant H-AChR ϵ-subunit expressed in Escherichia coli. HLA-DR3 transgenic 
      mice showed significantly higher clinical ocular and generalized MG severity 
      scores and lower grip strength values than HLA-DQ8 mice. H-AChR 
      ϵ-subunit-immunized HLA-DR3 transgenic mice had higher serum anti-AChR antibody 
      (IgG, IgG1, IgG2b, IgG2c and IgM) levels, neuromuscular junction IgG and 
      complement deposit percentages than ϵ-subunit-immunized HLA-DQ8 transgenic mice. 
      Control mice immunized with E. coli extract or complete Freund adjuvant (CFA) did 
      not show clinical and immunopathological features of ocular and generalized EAMG. 
      Lymph node cells of ϵ-subunit-immunized HLA-DR3 mice showed significantly higher 
      proliferative responses than those of ϵ-subunit-immunized HLA-DQ8 mice, crude E. 
      coli extract-immunized and CFA-immunized transgenic mice. Our results indicate 
      that the human AChR ϵ-subunit is capable of inducing myasthenic muscle weakness. 
      Diversity of the autoimmune responses displayed by mice expressing different HLA 
      class II molecules suggests that the interplay between HLA class II alleles and 
      AChR subunits might have a profound impact on the clinical course of MG.
CI  - Copyright (c) 2015 European Federation of Immunological Societies. Published by 
      Elsevier B.V. All rights reserved.
FAU - Wu, Xiaorong
AU  - Wu X
AD  - Department of Ophthalmology, First Affiliated Hospital, Nanchang University, 
      Nanchang 330006, PR China.
FAU - Tuzun, Erdem
AU  - Tuzun E
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX 77555-1070, USA.
FAU - Saini, Shamsher S
AU  - Saini SS
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX 77555-1070, USA.
FAU - Wang, Jun
AU  - Wang J
AD  - Second Department of Respiratory Disease, Jiangxi Provincial People's Hospital, 
      Nanchang, PR China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX 77555-1070, USA.
FAU - Aguilera-Aguirre, Leopoldo
AU  - Aguilera-Aguirre L
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX 77555-1070, USA.
FAU - Huda, Ruksana
AU  - Huda R
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX 77555-1070, USA.
FAU - Christadoss, Premkumar
AU  - Christadoss P
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX 77555-1070, USA. Electronic address: pchrista@utmb.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151019
PL  - Netherlands
TA  - Immunol Lett
JT  - Immunology letters
JID - 7910006
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, Cholinergic)
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Freund's Adjuvant/immunology
MH  - HLA-DQ Antigens/genetics/*immunology
MH  - HLA-DR3 Antigen/genetics/*immunology
MH  - Humans
MH  - Immunization/methods
MH  - Immunoglobulin G/blood/immunology
MH  - Immunoglobulin M/blood/immunology
MH  - Lymphocytes/immunology/pathology
MH  - Mice, Transgenic
MH  - Microscopy, Fluorescence
MH  - Myasthenia Gravis, Autoimmune, Experimental/chemically 
      induced/genetics/*immunology
MH  - Oculomotor Muscles/*immunology/metabolism/pathology
MH  - Protein Subunits/immunology
MH  - Receptors, Cholinergic/immunology
OTO - NOTNLM
OT  - Acetylcholine receptor
OT  - Autoimmunity
OT  - Epsilon subunit
OT  - Myasthenia gravis
OT  - Ocular myasthenia
EDAT- 2015/10/24 06:00
MHDA- 2016/09/28 06:00
CRDT- 2015/10/24 06:00
PHST- 2015/09/09 00:00 [received]
PHST- 2015/10/08 00:00 [revised]
PHST- 2015/10/13 00:00 [accepted]
PHST- 2015/10/24 06:00 [entrez]
PHST- 2015/10/24 06:00 [pubmed]
PHST- 2016/09/28 06:00 [medline]
AID - S0165-2478(15)30050-X [pii]
AID - 10.1016/j.imlet.2015.10.009 [doi]
PST - ppublish
SO  - Immunol Lett. 2015 Dec;168(2):306-12. doi: 10.1016/j.imlet.2015.10.009. Epub 2015 
      Oct 19.