Tag Archives: multiple sclerosis

Autoantibodies to myelin basic protein and histone H1 as immune biomarkers of neuropsychological disorders in patients with multiple sclerosis

S. Ya. Kyryliuk1, T. I. Nehrych1, N. K. Svyrydova2,
Ye. O. Trufanov2, R. S. Stoika3, Yu. Ya. Kit3

1Danylo Halytsky Lviv National Medical University, Ukraine;
2Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine;
3Institute of Cell Biology National Academy of Sciences of Ukraine, Lviv;
e-mail: sinitska@ukr.net

Received: 15 April 2020; Accepted: 13 November 2020

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with different disorders of neurological and higher cortical functions. It is important to identify biomarkers that can control the dynamics of neuropsychological changes and predict the progression of this process. The aim of the study was to investigate the pathogenic and clinical significance of serum autoantibodies to the myelin basic protein (MBP) and histone H1 in the occurrence of neurological and neuropsychological disorders in patients with MS. Fifty-five patients diagnosed for MS were examined. A general clinical and neurological examination, determination of cognitive status, depression level and the content of autoantibodies to histone H1 and MBP in the blood serum were conducted. Blood serum samples of 20 healthy volunteers were used in control.  The serum of patients with MS was shown to contain antibodies of IgG class to MBP and histone H1. The level of anti-histone H1 IgG-antibodies in blood serum of MS patients was found to be higher compared with the level of anti-MBP IgG-antibodies (P < 0.05). Increased levels of anti-MBP antibodies correlated with the severity of trunk ataxia, impaired conceptualization, and mood. High level of anti-histone H1 antibodies correlated with the severity of paresis, trunk ataxia, impaired conceptualization, semantic language, and mood. Determination of the level of anti-histone H1 antibodies in blood serum of patients with MS might serve as a biomarker of inflammatory and, probably, of the neurodegenerative processes of this disease and determine the dynamics of clinical course of the MS. Anti-MBP antibodies play an important role in the pathogenesis of the MS and are an additional marker of the severity of the clinical course of neurological and some neuropsychological disorders.

Freezing influences, the exposure of IgG glycans in sera from multiple sclerosis patients

M. Bozhenko1, M. Boichuk1, G. Bila2, T. Nehrych1*, R. Bilyy2*

1Department of Neurology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
2Department of Histology, Cytology and Embryology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
*e-mail: r.bilyy@gmail.com; tnehrych@gmail.com

Received: 08 January 2020; Accepted: 27 March 2020

N-glycan residues attached to Asn297 of the immunoglobulin IgG molecule are responsible for changing­ its structural conformation and are used as markers of many inflammatory diseases. Freezing stabilizes protein structure, while recent solution NMR data showed greatly altered IgG glycan mobility at different­ temperatures. The aim of the current work was to investigate whether freezing sera samples from multiple sclerosis (MS) patients and normal healthy donors (NHD) influences exposure of IgG glycans. The developed lectin immunosorbent assay was used to evaluate exposure of native IgG glycans with fucose-binding AAL lectin and sialic acid-binding SNA lectin. Sera samples were divided and either immediately frozen at -20 °C or stored at 4 °C. Lectin exposure was compared between 5 MS patient groups (n = 75) vs NHD (n = 23) and in paired samples with and without freezing. A significant increase in the exposure of fucose residues on IgG glycans in MS patients, compared to NHD, was observed. This increase was only observed if sera were frozen before analysis. The exposure of sialic acid was decreased in MS vs NHD samples after freezing sera samples. The exposure of core fucose residues and terminal sialic residues differed significantly in paired sera samples after freezing. Combined parameters of fucose and sialic acid exposure on native IgG glycans using frozen sera samples serve as a discriminative marker between MS and NHD. For AAL exposure, the discrimination of MS was characterized by AUROC of 0.906, sensitivity of 76.7% and specificity of 59.0% (P < 0.0001).

Use of vitamins for correction of the functional state of cytochrome P450 systems at experimental allergic encephalomyelitis

E. P. Pasichna1, G. V. Donchenko1, A. P. Burlaka2, V. S. Nedzvetskiy3,
E. P. Sidorik2, I. I.Ganusevich2, N. V. Delemenchuk1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
3Honchar National University, Dnipropetrovsk, Ukraine;
e-mail: ellapasich@gmail.com

It is known that inflammatory cytokines, which level is significantly increased in the pathogenesis of multiple sclerosis (MS), as well as interferon-β, which is used to treat autoimmune diseases, can inhibit cytochrome P450-dependent processes of detoxification and biotransformation. The uncontrolled decrease of the activity of these processes may have a negative affect on the state of patients, so it is urgent to study the functional state of the cytochrome P450 system and to develop effective means for its regulation in these conditions. The effect of vitamin D3 and efficiency of its composition with vitamins B1, B2, B6, PP, E, α-lipoic, α-linolenoic acid and mineral substances (Mg, Zn, Se) in prevention of a functional state changes of cytochrome P450- and b5-dependent systems of the rat brain and liver endoplasmic reticulum at EAE are investigated. It has been shown that the essential decrease of the level of these cytochromes is observed both in the brain and liver. In addition the level of activity of NADH-and NADPH-oxidoreductases, which are part of microsomal electron transport chain components and coupled with monooxigenases, was reduced. These changes confirm the disturbances of a redox state and functional activity of detoxication and biotransformation systems in the studied animal tissues. Supplement of vitamin D3 as well as the composition of biologically active substances, which we developed earlier, effectively eliminated the decrease of the level of cytochromes and activities of NADH-oxidoreductase in immunised rat tissues. Normalization of these disturbances can be explained by antioxidant and membrane-stabilizing properties of applied substances, and also by the ability to reduce the activity of inflammatory reactions by regulation of the level of inflammatory cytokines in rat organism at EAE. Thus the studied vitamin-mineral composition appeared to be more effective to normalize the found disturbances and it can be useful for prevention of exacerbations and for improvement of a status of patients with multiple sclerosis and other diseases, which are accompanied with hyperactivation of immune system.