Investigation of brain-derived neurotrophic factor and adhesion molecules in multiple sclerosis

BACKGROUND: In recent decades, numerous papers have been published exploring various biomarkers of multiple sclerosis in body fluids. Among these, particular attention should be given to brain-derived neurotrophic factor (BDNF), intercellular adhesion molecule 1 (ICAM1), neural cell adhesion molecule (NCAM), and the ratio of their concentrations in different types of multiple sclerosis progression.

AIM: The study aimed to analyze the diagnostic significance of BDNF, ICAM1, and NCAM in patients with different courses of multiple sclerosis.

METHODS: Blood sampling and assessment of clinical pattern of the disease course were performed in the study group (n = 66) and the control group consisting of healthy volunteers (n = 15). The study group patients were divided into three subgroups according to the type of the disease course: relapsing-remitting multiple sclerosis, both treated and non-treated with disease-modifying therapies (interferons β-1b), and secondary progressive multiple sclerosis. The severity of the patient disability was determined using the Expanded Disability Status Scale. The average annual frequency of exacerbations and the rate of the disease progression were calculated. Signs of progression were assessed based on the results of magnetic resonance imaging of the brain, spinal cord, and optic nerves. BDNF, ICAM1, and NCAM levels were measured using an enzyme-linked immunosorbent assay kit (Cloud-Clone, China) on a Multiskan GO analyzer (Thermo Fisher Scientific, Finland) with a Wellwash microplate washer (Thermo Fisher Scientific, Finland) and a PST-60HL-4 plate shaker/thermostat (Biosan, Latvia).

RESULTS: BDNF was increased in the blood serum in the study group patients (all subgroups) compared with the control group. Statistically significant differences were observed in patients receiving disease-modifying therapy. In the relapsing-remitting multiple sclerosis group, there was an inverse correlation between BDNF concentration and disability severity, as measured by the Expanded Disability Status Scale. Serum levels of NCAM were significantly increased in the relapsing-remitting multiple sclerosis subgroups treated and non-treated with disease-modifying therapies, as compared with the control group. In contrast, no statistically significant differences were found in serum levels of ICAM1 among patients in the study groups.

CONCLUSION: Increased levels of BDNF and NCAM in patients with relapsing-remitting multiple sclerosis with short disease duration may indicate the neuroprotective effect of these biomarkers, but may also serve as a predictor of disease exacerbation. High levels of BDNF during interferon β-1b therapy may indicate inadequate effectiveness of this drug, necessitating a decision to escalate therapy. In patients with secondary progressive multiple sclerosis, high levels of NCAM may be associated with increasing disability.