AsianScientist (Dec. 6, 2018) – In a study published in the Journal of Neuroimmunology, scientists in Japan have identified immune system targets that could lead to better treatments for a muscle-wasting condition known as myasthenia gravis.
In normal muscle tissues, movement is triggered when nerve endings release a neurotransmitter called acetylcholine, which binds to a receptor on muscle cells. This binding activates the muscle and causes it to contract.
Myasthenia gravis, or ‘grave muscle weakness,’ occurs when the immune system—which usually protects us from invading pathogens—mistakenly attacks the acetylcholine receptors needed for muscle movement. Controlling the immune response is therefore key to treating myasthenia gravis.
In the present study, researchers led by Associate Professor Kazuo Iwasa of Kanazawa University, Japan, investigated whether immune checkpoints—pathways that regulate the immune—could be harnessed for the treatment of myasthenia gravis.
“Programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, inhibit T-cell signaling and are extremely important for immunotolerance. Disruption of this pathway has been implicated in other autoimmune disorders, but its role in myasthenia gravis is unclear,” said Iwasa.
Using a specific fluorescent probe that binds to PD-L1, the research team showed that the ligand was more abundant in muscle tissues collected from myasthenia gravis patients compared with muscles from healthy individuals. By studying the gene expression in both normal and diseased tissues, they found that the PD-L1 gene was more highly expressed in diseased tissues.
Importantly, there was no difference between male and female patients, and gene expression was not influenced by the presence of tumors in the thymus, the organ responsible for the maturation of T-cells. However, the researchers noted a positive association between PD-L1 gene expression and disease severity.
“The unimodal relationship between PD-L1 gene expression and disease severity was particularly enlightening,” said study corresponding author Professor Masahito Yamada of Kanazawa University.
“As disease severity increases, so does PD-L1 expression in muscle cells, which may influence autoimmune reactivity and help to reduce or stabilize disease severity. Knowing this, we can potentially develop therapies targeting the PD-1 pathway to eliminate the symptoms of myasthenia gravis.”
The article can be found at: Iwasa et al. (2018) Programmed Cell Death Ligand 1 Expression is Upregulated in the Skeletal Muscle of Patients With Myasthenia Gravis.
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Source: Kanazawa University.
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