The blood-brain barrier may be impaired in Wilson disease (WD), according to a new study published in the Polish Journal of Neurology and Neurosurgery.
“In addition to copper toxicity, impaired immune functions might influence neurological advancement,” the authors of the study said and added that it is important to characterize inflammatory molecules and their relationship to neurological deterioration to help identify the best treatment option for patients.
Read more about the treatment of WD
The team measured the serum concentrations of markers for brain damage and blood-brain barrier dysfunction in patients with WD who were treated and untreated and assessed the correlations between any changes in these concentrations and neurological impairment.
The team analyzed 171 patients of whom 77 had hepatic disease and 94 had neurological disease. These patients were treated with a chelating agent for up to 15 years. The researchers compared these patients to 88 healthy controls.
They looked at the serum concentrations of intercellular adhesion molecule 1 (ICAM1) and P-selectin as markers of inflammation, matrix metallopeptidase 9 (MMP9), which is involved in the degradation of basement membranes and extracellular matrix proteins, glial fibrillary acidic protein (GFAP), a marker of damaged astrocytes, and S100 calcium-binding protein B (S100B), another marker of central nervous system injury, before and during treatment.
The results showed that the concentration of ICAM1 was higher before and during treatment compared to healthy controls. However, treatment resulted in a substantial decrease in all patients suggesting a reduction in inflammation.
The concentrations of P-selectin were high before treatment and stayed so during treatment independently of treatment duration and disease type, suggesting systemic inflammation.
The concentration of MMP9 was low before treatment suggesting active liver fibrosis and higher copper concentration but reached control levels during treatment.
The concentration of GFAP was high only in untreated patients who had neurological symptoms and in patients who were treated for longer compared to healthy controls. There was a significant drop in GFAP concentration during treatment but only in patients with neurological symptoms who were treated for a shorter duration. There were also no substantial changes in the concentration of S100B.
“Our results provide evidence of endothelial activation in WD,” the researchers concluded. “However, inconclusive GFAP results, and no increase in S100B, do not allow us to conclude whether the reactive gliosis is not prominent.”
Misztal M, Członkowska A, Cudna A, et al. Impact of treatment on blood-brain barrier impairment in Wilson’s disease. Neurol Neurochir Pol. Published online August 1, 2023. doi:10.5603/PJNNS.a2023.0053