Diabetes mellitus may worsen the aberrant humoral immunity in patients with myasthenia gravis by increasing the differentiation and function of T follicular helper cells, according to a new study published in the journal Clinical Immunology. Therefore, patients with myasthenia gravis and diabetes mellitus might benefit from tight glycemic control.

It was already known that diabetes mellitus was an independent risk factor for myasthenia gravis. However, the underlying mechanism of how the 2 conditions are linked was not clear, Tao Li, of the Shandong Provincial Qianfoshan Hospital in China, and colleagues noted.

In the present study, a team of researchers from China found that circulating T follicular helper cells were increased in patients with myasthenia gravis who also had diabetes mellitus. Moreover, these cells expressed high levels of inducible costimulators, a marker that is highly expressed when T cells are activated. 

Read more about the risk factors of myasthenia gravis

The researchers also found a positive correlation between activated circulating T follicular helper cells and plasmablasts, the precursors of plasma cells. 

Through in vitro experiments, they showed that long-term high glucose treatment promoted the differentiation and activation of T follicular helper cells, which, in turn, led to abnormal plasmablast differentiation and antibody secretion through the mechanistic target of the rapamycin signaling pathway. 

“However, the detailed mechanism about how high glucose regulates [mechanistic target of rapamycin complex 1] and [mechanistic target of rapamycin complex 2] activity in the development of [T follicular helper] cells needs to be further studied,” the researchers added.

Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction in which there is reduced electrical impulse transmission across the neuromuscular junction resulting in generalized fatigability and muscle weakness. The condition is dependent on T cells and is mediated by autoantibodies.

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia caused by the body not producing enough or not responding normally to insulin. Research suggests the condition has a significant impact on immune homeostasis. 

Reference

Li T, Yang C, Du T, et al. Diabetes mellitus aggravates humoral immune response in myasthenia gravis by promoting differentiation and activation of circulating Tfh cells. Clin Immunol. Published online October 25, 2022. doi:10.1016/j.clim.2022.109141