Abstract
Background and Objectives Complement regulatory proteins at the neuromuscular junction (NMJ) could offer protection against complement-mediated damage in myasthenia gravis (MG). However, there is limited information on their expression at the human NMJ. Thus, this study aimed at investigating the expression of the cluster of differentiation 59 (CD59) at the NMJ of human muscle specimens and demonstrating the overexpression of CD59 mRNA and protein in the muscles of patients with MG.
Methods In this observational study, muscle specimens from 16 patients with MG (9 and 7 patients with and without thymoma, respectively) and 6 nonmyopathy control patients were examined. Immunohistochemical stains, Western blot analysis, and quantitative real-time reverse transcription PCR were used to evaluate the CD59 expression.
Results A strong localized expression of CD59 was observed at the NMJ in both patients with and without MG. Moreover, the CD59/glyceraldehyde-3-phosphate dehydrogenase protein ratio in patients with MG was significantly higher than that in the nonmyopathy controls (MG; n = 16, median 0.16, interquartile range (IQR) 0.08–0.26 and nonmyopathy controls; n = 6, median 0.03, IQR 0.02–0.11, p = 0.01). The proportion of CD59 mRNA expression relative to AChR mRNA expression (ΔCtCD59/AChR) was associated with the quantitative MG score, MG activities of daily living score, and MG of Foundation of America Clinical Classification (r = 0.663, p = 0.01; r = 0.638, p = 0.014; and r = 0.715, p = 0.003, respectively).
Discussion CD59, which acts as a complement regulator, may protect the NMJ from complement attack. Our findings could provide a basis for further research that investigates the underlying pathogenesis in MG and the immunomodulating interactions of the muscle cells.
Glossary
- Ab=
- antibodies;
- ACh=
- acetylcholine;
- AChE=
- acetylcholinesterase;
- AChR=
- acetylcholine receptor;
- C=
- complement component;
- CD59=
- cluster of differentiation 59;
- Ct=
- cycles to threshold;
- GAPDH=
- glyceraldehyde-3-phosphate dehydrogenase;
- GPI=
- glycosylphosphatidylinositol;
- IgG=
- immunoglobulin G;
- IQR=
- interquartile range;
- MAC=
- membrane attack complex;
- MG=
- myasthenia gravis;
- MG-ADL=
- myasthenia gravis activities of daily living;
- MGFA=
- Myasthenia Gravis of Foundation of America;
- NMJ=
- neuromuscular junction;
- QMG=
- quantitative myasthenia gravis;
- qRT-PCR=
- quantitative real-time polymerase chain reaction;
- SPSS=
- Statistical Package for the Social Sciences;
- WB=
- western blotting;
- α-BTx=
- α-bungarotoxin
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
Submitted and externally peer reviewed. The handling editor was Marinos C. Dalakas, MD, FAAN.
- Received June 24, 2022.
- Accepted in final form September 19, 2022.
- Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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