Abstract
BackgroundNon–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.MethodsWe 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.ResultsWe 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).ConclusionsOur demonstration of elevated ACh levels in PBMCs of MG patients foreshadows potential new avenues for MG research and treatment.
Highlights
Non–neuronal acetylcholine (ACh) restricts autoimmune responses and attenuates inflammation by cholinergic anti-inflammation pathway
peripheral blood mononuclear cells (PBMCs)-derived ACh content changed in myasthenia gravis (MG) patients compared with controls We first established that UPLC-MS/MS was a precise, stable and available technique to detect intracellular ACh used this method routinely to determine the PBMC-derived ACh content of our MG patients
Eight patients were in each group, and the two groups showed no significant differences in quantitative MG (QMG) score (2.00 ± 1.604 vs. 1.75 ± 1.488, p = 0.7513)
Summary
Non–neuronal acetylcholine (ACh) restricts autoimmune responses and attenuates inflammation by cholinergic anti-inflammation pathway. Lymphocyte-derived ACh may play a key role in the interaction between the nervous system and immune system to restore homeostasis, a mechanism called the ‘cholinergic anti-inflammatory pathway’ [9, 10] Targeting this pathway, which reduces pro-inflammatory cytokine secretion, was effective in many experimental animal models, including inflammatory bowel disease [11], experimental autoimmune encephalomyelitis (EAE) [12,13,14,15,16], arthritis [17], ischemiareperfusion injury [18], sepsis [19, 20], pancreatitis [21], myocardial ischemia [22] and hemorrhagic shock [23]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
