Neutrophils, a type of white blood cell, may cause myasthenia gravis (MG) exacerbations through the secretion of a protein known as B-cell activating factor (BAFF), according to a study recently published in Advanced Science.
MG symptoms like muscle weakness and fatigue can become markedly more severe at times. The exact molecular causes of these exacerbations remain poorly understood.
Researchers sought to better understand what goes on in the body during these episodes of MG exacerbation. To do so, they performed single-cell RNA sequencing, a technique that helps examine disease mechanisms, on the cells of six patients with MG. Three of the patients had untreated MG in the stable phase; the other three patients were in the acute exacerbation phase.
Researchers focused on what took place specifically in neutrophils, which drastically increase in number during exacerbation episodes.
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The research team found that the secretion of BAFF by neutrophils is a key factor driving MG exacerbations. During acute exacerbations, mature neutrophils demonstrated higher levels of BAFF expression compared to stable disease phases. This observation supports the hypothesis that higher levels of BAFF secretion by neutrophils in MG contributes to the exacerbative disease state. In addition, researchers found the IFN-γ signaling pathway to be a driver of excessive BAFF secretion.
The findings explain why prior studies have found that therapies targeting BAFF have good clinical efficacy in patients with MG who have high levels of neutrophils.
“We have shown that neutrophils, through the secretion of BAFF, contribute to the progression and exacerbation of MG,” the authors of the study wrote. “Moreover, our study highlights the significant clinical implications of neutrophil-derived BAFF in MG treatment, emphasizing the potential for personalized therapeutic interventions.”
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