In mouse models of myasthenia gravis (MG), anti-acetylcholine receptor (AChR) antibodies can be quantified to monitor disease progression and treatment response. In mice, enzyme-linked immunosorbent assay (ELISA) is the gold standard to quantify these antibodies. However, this method requires antigen purification, which is both time-consuming and expensive. In humans, radioimmunoassay (RIA)-which is more sensitive than ELISA-is commonly used to quantify AChR antibodies. At present, however, no commercial RIA kits are available to quantify these antibodies in mice. The aim of this study was to compare a modified commercial human RIA kit to two ELISA methods to detect AChR antibodies in an experimental autoimmune mouse model of MG (EAMG). C57BL/6 J mice were immunized with purified AChR from Tetronarce californica (T-AChR). Serum samples were analyzed by RIA and two ELISAs (T-AChR and purified mouse AChR peptide [m-AChR]). The modified RIA showed excellent sensitivity (84.1 %) and specificity (100 %) for the detection of AChR antibodies. RIA showed a good agreement with T-AChR ELISA (κ = 0.69) but only moderate agreement with m-AChR ELISA (κ = 0.49). These results demonstrate the feasibility of modifying a commercially-available RIA kit to quantify AChR antibodies in EAMG. The advantage of this technique is that it eliminates the need to develop the entire methodology in-house and reduces inter and intra-laboratory variability.
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http://dx.doi.org/10.1016/j.jim.2024.113748 | DOI Listing |
Ann Neurosci
January 2025
Department of Neurology, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, India.
Background: Myasthenia gravis is an autoimmune neuromuscular disease primarily caused by autoantibodies against nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. However, extrathymic malignancies need to be considered in the elderly population.
Purpose: Although thymic malignancy is the most common tumour association, several extrathymic malignancies complicated with myasthenia gravis have been reported.
Int J Mol Sci
December 2024
Department of Neurology, Davis School of Medicine, University of California, 1515 Newton Court, Davis, CA 95618, USA.
We have designed and produced 39 amino acid peptide mimics of the and human acetylcholine receptors' (AChRs) main immunogenic regions (MIRs). These conformationally sensitive regions consist of three non-contiguous segments of the AChR α-subunits and are the target of 50-70% of the anti-AChR autoantibodies (Abs) in human myasthenic serum and in the serum of rats with a model of that disease, experimental autoimmune myasthenia gravis (EAMG), induced by immunizing the rats with the electric organ AChR. These MIR segments covalently joined together bind a significant fraction of the monoclonal antibodies (mAbs) raised in rats against electric organ AChR.
View Article and Find Full Text PDFMuscle Nerve
January 2025
Department of Neurology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, New York, USA.
Introduction/aims: Neonatal Fc receptor (FcRn) inhibitors represent a promising treatment option for patients with generalized myasthenia gravis (gMG); however, data on clinical use are limited. The aim of this report is to describe one center's approach to efgartigimod dosing in patients with gMG.
Methods: Medical records of patients with acetylcholine receptor antibody-positive (AChR-Ab+) gMG whose symptoms were not adequately controlled by oral medications and/or intravenous immunoglobulin who received efgartigimod between January 2022 and January 2024 were retrospectively evaluated.
Ther Adv Neurol Disord
December 2024
Department of Neurology, Faculty of Medicine, University of Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany.
In acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG), neonatal Fc-receptor (FcRn) inhibition has broadened the therapeutic spectrum. Myasthenic crisis (MC), heralded by an impending myasthenic crisis (iMC), is a critical condition requiring treatments with rapid onset and sustained efficacy. Currently treatments used for iMC, including intravenous immunoglobulins and plasma exchange/immunoadsorption, have limitations, such as delayed onset of action and potential side effects.
View Article and Find Full Text PDFBMJ Neurol Open
December 2024
Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Introduction: Myasthenia gravis (MG) is a T cell-dependent B cell-mediated autoimmune disease with pathogenic antibodies directed against components of the acetylcholine receptor (AChR). Current therapies do not address the root cause of the disease (autoimmune recognition of AChR) and are associated with possible serious side effects. Therefore, new therapeutic options targeting antigen-specific autoimmunity are needed.
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