Analysis of the hydrolysis of peptides of functionally important regions of brain and glial neurotrophic factors by antibodies of patients with schizophrenia and other neuroimmune diseases
Background. In certain neuroimmune diseases, such as schizophrenia, multiple sclerosis (MS), and systemic lupus erythematosus (SLE), the nervous and immune systems are simultaneously affected to varying degrees. Some neuroimmune diseases are accompanied by a decrease in the concentration of brain (BDNF) and glial (GDNF) neurotrophic factors, which may be due to a decrease in the formation or their excessive destruction in blood. The destruction may be associated with the action of proteolytic enzymes. Hypothesis: Recently discovered catalytic antibodies with proteolytic properties can bind and hydrolyze BDNF and GDNF. Objective: to analyze the hydrolysis level of peptides of functionally important regions of BDNF and GDNF by antibodies of patients with schizophrenia, MS and SLE. Material and Methods. The total (n=112) study sample included healthy volunteers (n=30), patients with schizophrenia (n=20), SLE (n=32) and MS (n=30). IgG preparations were isolated by affinity chromatography from serum. To analyze the peptidase activity of IgG preparations, we used four fluorescently labeled peptides, which are fragments of functionally important regions of BDNF and GDNF involved in binding to specific receptors. The level of relative activity of IgG preparations was determined by thin layer chromatography. Results. It was shown that IgG preparations of patients effectively hydrolyzed all analyzed peptides. The level of hydrolysis of all four peptides by IgG preparations of patients with schizophrenia, MS and SLE was statistically significantly (p<0.0001) higher than healthy donors. IgG preparations of patients with schizophrenia had the highest activity in the hydrolysis of three peptides. Conclusion. The data obtained indicate that catalytic antibodies specifically recognizing and hydrolyzing BDNF and GDNF peptides are formed in the analyzed neuroimmune diseases. Antibody-dependent hydrolysis of functionally important regions of BDNF and GDNF might disrupt the functioning of these neurotrophic factors. However, the effects of catalytic antibodies need to be tested on full-sized molecules of neurotrophic factors.