UCHL1, besides leptin and fibronectin, also could be a sensitive marker of the relapsing–remitting type of multiple sclerosis

Abstract

Research on the markers of immunoregulatory response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of leptin, fibronectin, and UCHL1 concentrations as potential biomarkers of a relapsing–remitting type of MS (RRMS). Surface Plasmon Resonance Imaging (SPRI) biosensors were used for the evaluation of proteins concentrations in 100 RRMS patients and 46 healthy volunteers. Plasma leptin, fibronectin, and UCHL1 concentrations were significantly higher in RRMS patients compared to the control group (p < 0.001, respectively). UCHL1 concentration evaluation revealed the highest diagnostic sensitivity (100%) and negative predictive value (100%) in differentiating MS patients from healthy individuals. There was no significant difference in the UCHL1 concentrations depending on the patient’s sex, the presence of relapse within the last 24 months, and the EDSS value (p > 0.05, respectively). In RRMS patients UCHL1 concentration positively correlated with fibronectin levels (r = 0.3928; p < 0.001). In the current cohort of patients plasma UCHL1 concentration was independent of the time of MS relapse and the severity of neurological symptoms. Thus current study may indicate that plasma UCHL1, besides leptin and fibronectin, also could be a promising high-sensitive potential biomarker of relapsing–remitting type of MS. However, these results should be validated with a larger group of patients, taking into account neuroimaging and cerebrospinal fluid analysis data, and by comparing them to patients with other neurological diseases as a control group.

The Comparison of the Selected Parameters of Brain Injury and Interleukins in the CSF in Patients Diagnosed De Novo with RRMS Compared to the Control Group

“…Moreover, it participates in the immune response, which might explain why the concentration of UCHL1 in patients diagnosed de novo with RRMS in our study correlated positively with the concentration of IL-2, known as a proinflammatory cytokine, and correlated positively with the concentration of IL-3, which is considered a multifunctional regulator of inflammation affecting immune cells and hematopoiesis [32,36,59].…”

“…Nevertheless, according to Górska et al, plasma UCHL1 could be a high-quality biomarker of RRMS. It was found that the plasma concentration of the enzyme was higher in RRMS patients compared to the control group, and it showed the highest diagnostic sensitivity (100%) compared to other markers in distinguishing MS patients from non-MS participants [32].…”

“…UCHL1 is a deubiquitinating enzyme of neuronal origin whose role in vivo remains partially unknown. However, its high content in neurons in the brain and spinal cord suggests that it plays a significant part in the normal activity of the nervous system [32,58]. The proteolytically stable protein seems to be involved in restoring the appropriate function of damaged axons and neurons [32].…”

“…Studies showed that the levels of this protein were increased in serum and CSF in patients after traumatic brain injury and were linked with the intensity of injury and long-term outcome [28][29][30][31]. The enzyme is expressed at high concentrations in neurons of the brain and spinal cord and plays a significant role in the normal functioning of the nervous system [32].…”