PMID- 37660538
OWN - NLM
STAT- MEDLINE
DCOM- 20240314
LR  - 20240321
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Linking)
VI  - 383
DP  - 2023 Oct 15
TI  - Silencing of FCRLB by shRNA ameliorates MuSK-induced EAMG in mice.
PG  - 578195
LID - S0165-5728(23)00181-9 [pii]
LID - 10.1016/j.jneuroim.2023.578195 [doi]
AB  - INTRODUCTION: Muscle specific kinase (MuSK) antibody positive myasthenia gravis 
      (MG) often presents with a severe disease course and resistance to treatment. 
      Treatment-refractory patients may respond to B cell depleting treatment methods. 
      Our aim was to investigate whether inhibition of Fc receptor-like B (FCRLB) could 
      effectively suppress autoimmunity without diminishing B cell counts in animal 
      model of MG, a classical antibody-mediated autoimmune disease. METHODS: 
      Experimental autoimmune MG was induced in Balb/C mice with two s.c. immunizations 
      with recombinant human MuSK in complete Freund's adjuvant. FCRLB was silenced 
      with a lentiviral particle transported shRNA in myasthenic mice with a single 
      i.p. injection during second MuSK-immunization. Control immunized mice received 
      scrambled shRNA or saline. Mice were observed for clinical parameters for 28 days 
      and at termination, anti-MuSK IgG, neuromuscular junction (NMJ) deposits, muscle 
      AChR expression and lymph node B and T cell ratios were assessed by ELISA, 
      immunofluorescence, immunoblotting and flow cytometry, respectively. RESULTS: 
      FCRLB shRNA-treated mice showed no muscle weakness or weight loss at termination. 
      Also, they exhibited higher grip strength and muscle AChR levels, lower anti-MuSK 
      IgG and NMJ IgG/C3 levels than control mice. Flow cytometry analysis showed that 
      ratios of major effector lymph node B and T cell populations were not altered by 
      FCRLB silencing. However, regulatory T and CD19 + CD5+ B cell ratios were 
      decreased in FCRLB shRNA-group. CONCLUSION: Our results provide evidence 
      regarding involvement and therapeutic value of FCRLB in MuSK-MG. Silencing of 
      FCRLB appears to substantially inhibit antibody production without interfering 
      with survival of major lymphocyte populations.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Koral, Gizem
AU  - Koral G
AD  - Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, 
      Istanbul University, Istanbul, Turkey.
FAU - Ulusoy, Canan
AU  - Ulusoy C
AD  - Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, 
      Istanbul University, Istanbul, Turkey.
FAU - Cossins, Judith
AU  - Cossins J
AD  - Neuromuscular Disorders Group, Nuffield Department of Clinical Neurosciences, 
      Weatherall Institute of Molecular Medicine, Oxford, UK.
FAU - Lazaridis, Konstantinos
AU  - Lazaridis K
AD  - Department of Immunology, Hellenic Pasteur Institute, Athens, Greece.
FAU - Turkoglu, Recai
AU  - Turkoglu R
AD  - Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
FAU - Dong, Yin Yao
AU  - Dong YY
AD  - Neuromuscular Disorders Group, Nuffield Department of Clinical Neurosciences, 
      Weatherall Institute of Molecular Medicine, Oxford, UK.
FAU - Tuzun, Erdem
AU  - Tuzun E
AD  - Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, 
      Istanbul University, Istanbul, Turkey.
FAU - Yilmaz, Vuslat
AU  - Yilmaz V
AD  - Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, 
      Istanbul University, Istanbul, Turkey. Electronic address: vuslaty@hotmail.com.
LA  - eng
GR  - MR/S007180/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230830
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Immunoglobulin G)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - 0 (Autoantibodies)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Immunoglobulin G
MH  - Receptor Protein-Tyrosine Kinases
MH  - Neuromuscular Junction
MH  - Immunization/methods
MH  - *Myasthenia Gravis, Autoimmune, Experimental
MH  - Autoantibodies
OTO - NOTNLM
OT  - Autoimmunity
OT  - FCRLB
OT  - Muscle specific kinase
OT  - Myasthenia gravis
OT  - shRNA
COIS- Declaration of Competing Interest The authors declare no disclosures of any 
      financial interest.
EDAT- 2023/09/04 00:41
MHDA- 2024/03/14 06:47
CRDT- 2023/09/03 18:06
PHST- 2023/03/04 00:00 [received]
PHST- 2023/05/18 00:00 [revised]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2024/03/14 06:47 [medline]
PHST- 2023/09/04 00:41 [pubmed]
PHST- 2023/09/03 18:06 [entrez]
AID - S0165-5728(23)00181-9 [pii]
AID - 10.1016/j.jneuroim.2023.578195 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2023 Oct 15;383:578195. doi: 10.1016/j.jneuroim.2023.578195. Epub 
      2023 Aug 30.