Nav: Home

Immune checkpoints could be key to treating autoimmune disease myasthenia gravis

November 30, 2018

Kanazawa, Japan - Quite literally meaning "grave muscle weakness", myasthenia gravis is a chronic autoimmune disorder that causes serious weakening of skeletal muscles responsible for movements such as ocular motion, eye-opening, swallowing, and breathing. Although symptoms can be controlled, there is currently no cure for this potentially debilitating disease.

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 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.

Bearing this in mind, researchers at Kanazawa University investigated whether pathways that regulate the immune response, known as immune checkpoints, could be harnessed for the treatment of myasthenia gravis. Publishing their findings in a recent issue of the Journal of Neuroimmunology, lead author Kazuo Iwasa describes the rationale behind the study: "Inhibitory checkpoint molecule 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."

Using a specific fluorescent antibody, or marker, 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. Studying gene expression in these tissues confirmed their initial findings, with results showing that the PD-L1 gene was more highly expressed in patient 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, there did appear to be a reciprocal association between PD-L1 gene expression and disease severity.

"The unimodal relationship between PD-L1 gene expression and disease severity was particularly enlightening," says study corresponding author Masahito Yamada. "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."
-end-


Kanazawa University

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...