Related Experiment Video
Updated: Jul 4, 2026

Characterization of Neuromuscular Junctions in Mice by Combined Confocal and Super-Resolution Microscopy
Published on: December 8, 2021
Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis
Ming Gu1, Maria Kakoulidou, Ricardo Giscombe
1Department of Medicine, Rheumatological Research Unit, CMM, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness induced by autoantibodies against the acetylcholine receptor. CTLA-4 (CD152) plays an inhibitory role in the immune response and has been suggested to be involved in the pathophysiology of MG. In this study, we focused on alternative CTLA-4 mRNA expression in PBMCs from MG patients. We defined two new isoforms of CTLA-4 mRNA that arise due to alternative splicing. By semi-quantitative RT-PCR analysis, we observed a lower expression of sCTLA-4 mRNA relative to the membrane form in MG patients. In addition, the MG patients had lower levels of sCTLA-4 mRNA in PBMCs compared to healthy controls, as assessed by real-time PCR. One of the spliced isoforms (LCTLA-4) was more prevalent in MG patients compared to healthy controls. The alternative splicing was not associated with sex, thymectomy, serum levels of anti-AChR, immunosuppressive treatment or the four CTLA-4 gene polymorphisms analyzed. This study reveals an abnormal spectrum of mRNA expression of CTLA-4 in MG patients, which marks the importance of studying gene expression of alternative splicing.
Related Concept Videos
Myasthenia Gravis ll: Pathophysiology
Myasthenia Gravis: Diagnostic Tests
The edrophonium test is a diagnostic tool for myasthenia gravis. It involves...
Myasthenia Gravis: Overview and Treatment
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which leads...
Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
RNA Splicing
