PMID- 36240543
OWN - NLM
STAT- MEDLINE
DCOM- 20221205
LR  - 20230111
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Linking)
VI  - 373
DP  - 2022 Dec 15
TI  - Enrichment of serum IgG4 in MuSK myasthenia gravis patients.
PG  - 577978
LID - S0165-5728(22)00173-4 [pii]
LID - 10.1016/j.jneuroim.2022.577978 [doi]
AB  - Muscle-specific kinase (MuSK) myasthenia gravis (MG) is a neuromuscular 
      autoimmune disease belonging to a growing group of IgG4 autoimmune diseases 
      (IgG4-AIDs), in which the majority of pathogenic autoantibodies are of the IgG4 
      subclass. The more prevalent form of MG with acetylcholine receptor (AChR) 
      antibodies is caused by IgG1-3 autoantibodies. A dominant role for IgG4 in 
      autoimmune disease is intriguing due to its anti-inflammatory characteristics. It 
      is unclear why MuSK autoantibodies are predominantly IgG4. We hypothesized that 
      MuSK MG patients have a general predisposition to generate IgG4 responses, 
      therefore resulting in high levels of circulating IgG4. To investigate this, we 
      quantified serum Ig isotypes and IgG subclasses using nephelometric and 
      turbidimetric assays in MuSK MG and AChR MG patients not under influence of 
      immunosuppressive treatment. Absolute serum IgG1 was increased in both MuSK and 
      AChR MG patients compared to healthy donors. In addition, only MuSK MG patients 
      on average had significantly increased and enriched serum IgG4. Although more 
      MuSK MG patients had elevated serum IgG4, for most the IgG4 serum levels fell 
      within the normal range. Correlation analyses suggest MuSK-specific antibodies do 
      not solely explain the variation in IgG4 levels. In conclusion, although serum 
      IgG4 levels are slightly increased, the levels do not support ubiquitous IgG4 
      responses in MuSK MG patients as the underlying cause of dominant IgG4 MuSK 
      antibodies.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Vergoossen, Dana L E
AU  - Vergoossen DLE
AD  - Department of Human Genetics, Leiden University Medical Centre LUMC, Einthovenweg 
      20, 2300 RC Leiden, the Netherlands.
FAU - Ruiter, Annabel M
AU  - Ruiter AM
AD  - Department of Neurology, Leiden University Medical Centre LUMC, Albinusdreef 2, 
      2333 ZA Leiden, the Netherlands.
FAU - Keene, Kevin R
AU  - Keene KR
AD  - Department of Neurology, Leiden University Medical Centre LUMC, Albinusdreef 2, 
      2333 ZA Leiden, the Netherlands.
FAU - Niks, Erik H
AU  - Niks EH
AD  - Department of Neurology, Leiden University Medical Centre LUMC, Albinusdreef 2, 
      2333 ZA Leiden, the Netherlands.
FAU - Tannemaat, Martijn R
AU  - Tannemaat MR
AD  - Department of Neurology, Leiden University Medical Centre LUMC, Albinusdreef 2, 
      2333 ZA Leiden, the Netherlands.
FAU - Strijbos, Ellen
AU  - Strijbos E
AD  - Department of Neurology, Leiden University Medical Centre LUMC, Albinusdreef 2, 
      2333 ZA Leiden, the Netherlands.
FAU - Lipka, Alexander F
AU  - Lipka AF
AD  - Department of Neurology, Leiden University Medical Centre LUMC, Albinusdreef 2, 
      2333 ZA Leiden, the Netherlands.
FAU - van der Zijde, Els C Jol
AU  - van der Zijde ECJ
AD  - Willem-Alexander Children's Hospital, Leiden University Medical Centre LUMC, 
      Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
FAU - van Tol, Maarten J D
AU  - van Tol MJD
AD  - Willem-Alexander Children's Hospital, Leiden University Medical Centre LUMC, 
      Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
FAU - Bakker, Jaap A
AU  - Bakker JA
AD  - Department of Clinical Chemistry, Leiden University Medical Centre LUMC, 
      Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
FAU - Wevers, Brigitte A
AU  - Wevers BA
AD  - Department of Clinical Chemistry, Leiden University Medical Centre LUMC, 
      Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
FAU - Westerberg, Elisabet
AU  - Westerberg E
AD  - Clinical Neurophysiology, Department of Medical Sciences, Uppsala University, 
      Akademiska sjukhuset, Ingang 85, 3rd floor, 751 85 Uppsala, Sweden.
FAU - Borges, Lucia S
AU  - Borges LS
AD  - Department of Neurology, University of California Davis, 1515 Newton Court, 
      Davis, CA 95618, USA.
FAU - Tong, Olivia C
AU  - Tong OC
AD  - Department of Neurology, University of California Davis, 1515 Newton Court, 
      Davis, CA 95618, USA.
FAU - Richman, David P
AU  - Richman DP
AD  - Department of Neurology, University of California Davis, 1515 Newton Court, 
      Davis, CA 95618, USA.
FAU - Illa, Isabel
AU  - Illa I
AD  - Neuromuscular diseases Neurology department, Hospital Sant Pau UAB, Avenida Pare 
      Claret N degrees  167, Barcelona 08025, Spain.
FAU - Punga, Anna Rostedt
AU  - Punga AR
AD  - Clinical Neurophysiology, Department of Medical Sciences, Uppsala University, 
      Akademiska sjukhuset, Ingang 85, 3rd floor, 751 85 Uppsala, Sweden.
FAU - Evoli, Amelia
AU  - Evoli A
AD  - Department of Neurology, Universita Cattolica del Sacro Cuore, Largo A. Gemelli 
      1, 00168 Rome, Italy.
FAU - van der Maarel, Silvere M
AU  - van der Maarel SM
AD  - Department of Human Genetics, Leiden University Medical Centre LUMC, Einthovenweg 
      20, 2300 RC Leiden, the Netherlands.
FAU - Verschuuren, Jan J
AU  - Verschuuren JJ
AD  - Department of Neurology, Leiden University Medical Centre LUMC, Albinusdreef 2, 
      2333 ZA Leiden, the Netherlands.
FAU - Huijbers, Maartje G
AU  - Huijbers MG
AD  - Department of Human Genetics, Leiden University Medical Centre LUMC, Einthovenweg 
      20, 2300 RC Leiden, the Netherlands; Department of Neurology, Leiden University 
      Medical Centre LUMC, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. Electronic 
      address: M.G.M.Huijbers@lumc.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221007
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Humans
MH  - Autoantibodies
MH  - *Immunoglobulin G
MH  - *Myasthenia Gravis
OTO - NOTNLM
OT  - Autoimmune disease
OT  - IgG4
OT  - Immunoglobulins
OT  - MuSK
OT  - Myasthenia gravis
OT  - Serum
COIS- Declaration of Competing Interest OT, LB and DR receive research support from NIH 
      and Cabaletta Biopharma. JV, SM, MH are co-inventors on MuSK-related patents. 
      LUMC and JV, SM and MH receive royalties from these patents. LUMC receives 
      royalties on a MuSK ELISA. JV is consultant for Argenx, Alexion, NMD Pharma. ARP 
      is consultant for Argenx. MH receives financial support from the LUMC (OIO 2017, 
      Gisela Their Fellowship 2021), Top Sector Life Sciences & Health to Samenwerkende 
      Gezondheidsfondsen (LSHM18055-SGF and LSHM19130), Prinses Beatrix Spierfonds 
      (W.OR-19.13). The remaining authors declare no interests. The LUMC is part of the 
      European Reference Network for Rare Neuromuscular Diseases [ERN EURO-NMD] and the 
      Netherlands Neuromuscular Center.
EDAT- 2022/10/15 06:00
MHDA- 2022/12/03 06:00
CRDT- 2022/10/14 18:14
PHST- 2022/08/20 00:00 [received]
PHST- 2022/09/26 00:00 [revised]
PHST- 2022/10/05 00:00 [accepted]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/12/03 06:00 [medline]
PHST- 2022/10/14 18:14 [entrez]
AID - S0165-5728(22)00173-4 [pii]
AID - 10.1016/j.jneuroim.2022.577978 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2022 Dec 15;373:577978. doi: 10.1016/j.jneuroim.2022.577978. Epub 
      2022 Oct 7.