Non-neuronal cholinergic activity is potentiated in myasthenia gravis.
BACKGROUND
Non-neuronal acetylcholine (ACh) restricts autoimmune responses and attenuates inflammation by cholinergic anti-inflammation pathway. To date, the implication of ACh in myasthenia gravis (MG) remained unexplored. This study aimed to investigate the possible relationship between ACh levels, anti-muscle-specific tyrosine kinase (MuSK) antibody titers, main clinical features and outcomes of MG patients.


METHODS
We successfully measured ACh levels in human peripheral blood mononuclear cells (PBMCs) from 125 MG patients and 50 matched healthy controls by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We assessed the quantitative MG (QMG) scores for each patient and titered anti-MuSK antibody.


RESULTS
We found that PBMC-derived ACh level was significantly higher in MG patients, especially in patients of class III, IV-V, compared with that in controls (0.142 ± 0.108 vs. 0.075 ± 0.014 ng/million cells, p = 0.0003) according to the Myasthenia Gravis Foundation of America clinical classification. Importantly, we also found that ACh levels were positively correlated with QMG scores (r = 0.83, p < 0.0001) and anti-MuSK Ab levels (r = 0.85, p < 0.0001).


CONCLUSIONS
Our demonstration of elevated ACh levels in PBMCs of MG patients foreshadows potential new avenues for MG research and treatment.
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Bin
B
Han
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Chao
C
Zhang
Department of Neurology, Tianjin HuanHu Hospital, Tianjin, 300060, China.
Shoufeng
S
Liu
Laboratory of Physical and Chemical Research, Tianjin Centers for Disease Control and Prevention, Tianjin, 300011, China.
Yiping
Y
Xia
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China.
Hao
H
Sun
Department of Neurology, Tianjin First Center Hospital, Tianjin Medical University, Tianjin, 300192, China.
Zhongying
Z
Gong
Département de chimie et biochimie, Université de Moncton, Moncton, New Brunswick, E1A 3E9, Canada.
Alain R
AR
Simard
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.|Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA.
Qiang
Q
Liu
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. hjw@tmu.edu.cn.
Junwei
J
Hao
D000109:Acetylcholine / Q000097:blood*; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood; D011950:Receptors, Cholinergic / Q000097:blood; D053719:Tandem Mass Spectrometry
D001323:Autoantibodies; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000109:Acetylcholine
Acetylcholine; Cholinergic anti-inflammatory pathway; Inflammation; Myasthenia gravis