Yale Scientist Named MGNet Scholar Will Study MG Immune Mechanisms

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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This year’s MGNet Scholar award, funded by the Myasthenia Gravis Rare Disease Network (MGNet), has gone to a scientist at Yale University who is investigating the immune mechanisms behind the development of myasthenia gravis (MG) in people who have been treated with a type of immunotherapy.

The awardee is Gianvito Masi, MD, a neurologist in the lab of Kevin O’Connor, PhD, at the Yale School of Medicine, in Connecticut.

Totaling up to $75,000 per year, the award will support Masi’s salary and research costs for a period of two years, starting in June 2022. There is an additional $3,000 per year available to provide the awardee the opportunity to travel to MGNet sites to collaborate with peers, learn specific skills, and share research findings.

Scientists previously have found a link between autoimmunity, which occurs when the body’s immune system mistakes its own healthy tissues as foreign and attacks them, and MG. O’Connor’s current work focuses on how B-cells — a type of antibody-producing immune cell — trigger and sustain autoimmunity.

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His team found that MG patients have defects in B-cell tolerance checkpoints, a type of “brake” that controls how strong and how good a person’s immune response is.

Now, Masi hopes to gain clarity on the immune mechanisms of a recently identified form of MG that is induced by immune checkpoint inhibitors, a type of immunotherapy that leverages the power of the immune system to destroy cancer cells.

“Positioned at the intersection of neurology, immunology and oncology, this project aims to evaluate B-cell tolerance defects and autoantibody functionality in patients who develop MG following cancer immunotherapy,” Masi said in a university press release. “This research topic promises a new window onto the pathogenesis [disease development] of MG, with further implications for the care of MG patients.”

Part of the immune system, immune checkpoint proteins help keep an immune response from being too strong — to the level that it destroys healthy cells in the body. However, when these immune checkpoint proteins bind to other proteins on cancer cells, they also can prevent the immune system from killing cancer cells.

Immune checkpoint inhibitors work by blocking checkpoint proteins from binding to their partner proteins. This prevents immune cells from being shut down when encountering cancer cells.

However, immune checkpoint inhibitors can cause side effects, mostly related to the activity of the immune system. Rare cases of immune checkpoint inhibitor-induced MG have been reported. Knowing how immune checkpoint inhibitors induce MG is important to improve patient outcomes.