Patients with myasthenia gravis (MG) have increased plasma concentration of matrix metalloproteinase-9 (MMP-9) but reduced plasma levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases (TIMPs), according to a new study published in the journal Brain Sciences. The study also showed a positive correlation between the concentration of MMP-2 and the severity of the disease.

MMPs and TIMPs could play a role in the pathogenesis of MG and be associated with the risk of clinical deterioration, Vincenzo Di Stefano, MD, of the University of Palermo in Italy, and colleagues noted.

Many researchers have proposed MMPs and TIMPs as promising biomarkers in a number of immune-mediated disorders. 

Read more about the types of myasthenia gravis

Here, the investigators measured the plasma levels of MMP-9 and MMP-2 and their tissue inhibitors in a group of 14 patients with generalized MG. They then compared these levels to the levels in the plasma of 13 age-matched healthy controls.

The levels of MMP-9 were higher in the plasma of patients with MG compared to healthy controls, while the levels of MMP-2 were lower. Similarly, the ratio of MMP-9 over its inhibitor was higher, while the ratio of MMP-2 over its inhibitor was lower in patients with MG compared to controls. 

The researchers also found that higher levels of MMP-2 were associated with greater disease severity as measured by the modified Osserman classification index.

“Our preliminary results may support the hypothesis that plasma levels of metalloproteinases and their inhibitors might play a role in the pathogenesis of generalized MG,” the researchers wrote.

“However, future studies should be performed in wider groups of patients before and after treatment, both to confirm our findings and to assess the potential usefulness of MMPs and TIMPs evaluations as indicators of treatment response,” they concluded.


Di Stefano V, Tubiolo C, Gagliardo A, et al. Metalloproteinases and tissue inhibitors in generalized myasthenia gravis: a preliminary study. Brain Sci. Published online October 26, 2022. doi:10.3390/brainsci12111439