TY - JOUR

T1 - Catalytic antibodies as a new evidence of the humoral immune system dysfunction in schizophrenia

AU - Ermakov, E.

AU - Ivanova, S.

AU - Semke, A.

AU - Dmitrenok, P.

AU - Buneva, V.

AU - Nevinsky, G.

PY - 2019

Y1 - 2019

N2 - Background: Schizophrenia is known to be associated with imbalance in the neurotransmitter system and with dysregulation of both innate and adaptive immune systems [1]. Neuroinflammation in the perinatal and neonatal period can lead to a neurodevelopmental abnormalities, violation of synaptic plasticity and synaptic pruning in the adulthood [2]. Also, microRNAs are involved in the regulation of neuronal development, as well as immune response. The microRNA expression profiles in the bloodstream and in the different brain regions are altered in schizophrenia. It is shown that a change in the levels of microRNAs can alter the behavior [3]. Recently catalytic antibodies (abzymes) that not only binding DNA but also hydrolyze this molecule were revealed in the serum of patients with schizophrenia [4]. It has been shown that the formation of catalytic antibodies is one of the early signs of humoral immune system pathology [5]. We hypothesized that catalytic antibodies can hydrolyze not only DNA but also microRNAs and can participate in the pathogenesis of schizophrenia. Objective: To investigate disturbances in the humoral immune system of patients with schizophrenia, in particular a) IgG subclasses, IgA and IgM level and ratio in serum of patients; b) molecular structure of light and heavy chains of IgG; c) ability of IgG antibodies to hydrolyze the neurospecific microRNAs. Methods: In our study, 35 patients (17 men and 18 women) with a verified diagnosis of paranoid schizophrenia and 22 healthy donors (10 men and 12 women) were included. The average age in the group of patients was 35.8±8.9 years, duration of disease – 9.1±5.4 years. IgG1, IgG2, IgG3, IgG4, IgA and IgM levels was determined by ELISA. IgG structure analysis was performed using MALDI-TOF mass spectrometry. Electrophoretically and immunologically homogeneous IgG preparations were obtained by affinity chromatography of the serum proteins. The microRNA-hydrolyzing activity of IgG was detected by the level of hydrolysis of four neuro-specific fluorescently labeled microRNAs (miR-137, miR-219a-2-3p, miR-219a-5p and miR-9-5p). The products of the hydrolysis were analyzed by PAGE under denaturing conditions using laser scanner. Statistical analysis was carried out using the Mann — Whitney U-test in the Statistica 10 software. Results: A decrease in the IgG1 and IgG2 subclasses level was found in patients with schizophrenia as compared with healthy donors (p

AB - Background: Schizophrenia is known to be associated with imbalance in the neurotransmitter system and with dysregulation of both innate and adaptive immune systems [1]. Neuroinflammation in the perinatal and neonatal period can lead to a neurodevelopmental abnormalities, violation of synaptic plasticity and synaptic pruning in the adulthood [2]. Also, microRNAs are involved in the regulation of neuronal development, as well as immune response. The microRNA expression profiles in the bloodstream and in the different brain regions are altered in schizophrenia. It is shown that a change in the levels of microRNAs can alter the behavior [3]. Recently catalytic antibodies (abzymes) that not only binding DNA but also hydrolyze this molecule were revealed in the serum of patients with schizophrenia [4]. It has been shown that the formation of catalytic antibodies is one of the early signs of humoral immune system pathology [5]. We hypothesized that catalytic antibodies can hydrolyze not only DNA but also microRNAs and can participate in the pathogenesis of schizophrenia. Objective: To investigate disturbances in the humoral immune system of patients with schizophrenia, in particular a) IgG subclasses, IgA and IgM level and ratio in serum of patients; b) molecular structure of light and heavy chains of IgG; c) ability of IgG antibodies to hydrolyze the neurospecific microRNAs. Methods: In our study, 35 patients (17 men and 18 women) with a verified diagnosis of paranoid schizophrenia and 22 healthy donors (10 men and 12 women) were included. The average age in the group of patients was 35.8±8.9 years, duration of disease – 9.1±5.4 years. IgG1, IgG2, IgG3, IgG4, IgA and IgM levels was determined by ELISA. IgG structure analysis was performed using MALDI-TOF mass spectrometry. Electrophoretically and immunologically homogeneous IgG preparations were obtained by affinity chromatography of the serum proteins. The microRNA-hydrolyzing activity of IgG was detected by the level of hydrolysis of four neuro-specific fluorescently labeled microRNAs (miR-137, miR-219a-2-3p, miR-219a-5p and miR-9-5p). The products of the hydrolysis were analyzed by PAGE under denaturing conditions using laser scanner. Statistical analysis was carried out using the Mann — Whitney U-test in the Statistica 10 software. Results: A decrease in the IgG1 and IgG2 subclasses level was found in patients with schizophrenia as compared with healthy donors (p

UR - https://www.mendeley.com/catalogue/36e0df17-6004-3fe0-9af8-f7198a6a47c9/

U2 - 10.1016/j.euroneuro.2018.11.867

DO - 10.1016/j.euroneuro.2018.11.867

M3 - Meeting Abstract

VL - 29

SP - S586-S586

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

T2 - 31st Congress of the European-College-of-Neuropsychopharmacology (ECNP)

Y2 - 6 October 2018 through 9 October 2018

ER -