Autoantibodies in HIV‐infected patients: Cross site‐specific hydrolysis of H1 histone and myelin basic protein

BioFactors ◽  
2018 ◽  
Vol 45 (2) ◽  
pp. 211-222 ◽  
Author(s):  
Svetlana V. Baranova ◽  
Pavel S. Dmitrienok ◽  
Valentina N. Buneva ◽  
Georgy A. Nevinsky
Keyword(s):  
Myelin Basic Protein ◽  
Basic Protein ◽  
Site Specific ◽  
H1 Histone ◽  
Hydrolysis Of ◽  
Cross Site

scholarly journals HIV-Infected Patients: Cross Site-Specific Hydrolysis of H3 and H4 Histones and Myelin Basic Protein with Antibodies against These Three Proteins

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 316
Author(s):  
Svetlana V. Baranova ◽  
Pavel S. Dmitrenok ◽  
Valentina N. Buneva ◽  
Sergey E. Sedykh ◽  
Georgy A. Nevinsky
Keyword(s):  
Myelin Basic Protein ◽  
Intercellular Space ◽  
Basic Protein ◽  
Cross Reactivity ◽  
Cleavage Sites ◽  
Site Specific ◽  
Protein Clusters ◽  
Negative Role ◽  
Toxic Responses ◽  
Hydrolysis Of

Histones play important roles in chromatin functioning and gene transcription, but in the intercellular space, they are harmful since they stimulate systemic inflammatory and toxic responses. Electrophoretically homogeneous IgGs against myelin basic protein (MBP), as well as H3 and H4 histones, were isolated from sera of HIV-infected patients. In contrast to known classical proteases, these IgGs split exclusively only histones and MBP but no other control proteins. Among 13 sites of hydrolysis of H3 by IgGs against H3 and 14 sites for anti-MBP IgGs, only two sites of the hydrolysis were the same. Between seven cleavage sites of H4 with IgGs against H4 and 9 sites of this histone hydrolysis by antibodies against MBP, only three sites were the same. The sites of hydrolysis of H3 (and H4) with abzymes against these histones and against MBP were different, but several expended protein clusters containing hydrolysis sites are partially overlapped. The existence of enzymatic cross-reactivity of abzymes against H3 and H4 and MBP represents a great menace to humans since due to cell apoptosis, histones constantly occur in human blood. They can hydrolyze MBP of the myelin sheath of axons and play a negative role in the pathogenesis of HIV-infected patients.

scholarly journals Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1140
Author(s):  
Georgy A. Nevinsky ◽  
Svetlana V. Baranova ◽  
Valentina N. Buneva ◽  
Pavel S. Dmitrenok
Keyword(s):  
Multiple Sclerosis ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Maldi Mass Spectrometry ◽  
High Rate ◽  
H1 Histone ◽  
Constituent Element ◽  
Negative Role ◽  
Rate Of Hydrolysis ◽  
Hydrolysis Of

Histones play a key role in chromatin remodeling and gene transcription. Further, free histones in the blood act as damage-associated molecules. Administration of histones to animals results in systemic inflammatory and toxic effects. Myelin basic protein is the principal constituent element of the myelin-proteolipid sheath of axons. Abzymes (antibodies with catalytic activities) are the original features of some autoimmune diseases. In this study, electrophoretically homogeneous IgGs against H1, H2A, H2B, H3, and H4 histones and myelin basic protein (MBP) were isolated from the blood sera of multiple sclerosis (MS) patients by several affinity chromatographies. Using MALDI mass spectrometry, the sites of H1 histone cleavage by IgGs against H1, H2A, H2B, H3, H4, and MBP were determined. It was shown that IgGs against H1 split H1 at 12 sites, while the number of cleavage sites by abzymes against other histones was lower: H2A (9), H2B (7), H3 (3), and H4 (3). The minimum rate of H1 hydrolysis was observed for antibodies against H3 and H4. A high rate of hydrolysis and the maximum number of H1 hydrolysis sites (17) were found for antibodies against MBP. Only a few sites of H1 hydrolysis by anti-H1 antibodies coincided with those for IgGs against H2A, H2B, H3, H4, and MBP. Thus, the polyreactivity of complexation and the enzymatic cross-activity of antibodies against H1, four other histones, and MBP have first been shown. Since histones act as damage molecules, abzymes against histones and MBP can play a negative role in the pathogenesis of MS and probably other different diseases as well.

scholarly journals Extreme Diversity of IgGs Against Histones, DNA, and Myelin Basic Protein in the Cerebrospinal Fluid and Blood of Patients with Multiple Sclerosis

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 630 ◽  
Author(s):  
Irina A. Kostrikina ◽  
Valentina N. Buneva ◽  
Enrico Granieri ◽  
Georgy A. Nevinsky
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Relative Concentration ◽  
Correlation Coefficients ◽  
Hydrolysis Of ◽  
Hydrolysis Of Dna

It was recently shown that IgGs from sera of multiple sclerosis (MS) patients are active in the hydrolysis of DNA and myelin basic protein (MBP). We first analyzed the relative concentration of antibodies against five histones (H1, H2a, H2b, H3, and H4) in the cerebrospinal fluid (CSF) and serum of patients with MS. The relative concentrations of blood and CSF IgGs against histones and their activity in the hydrolysis of five histones varied greatly from patient to patient. However, all 28 IgG preparations were hydrolyzed from one to five histones. Relative activities and correlation coefficients among the activities of IgGs from serum and CSF in the hydrolysis of five histones (H1, H2a, H2b, H3, and H4), DNA, and MBP were calculated. It was shown that auto-IgGs from CSF and sera of MS patients are extremely heterogeneous in their affinity to histones, MBP, and DNA. The heterogeneity of IgG-abzymes hydrolyzing DNA, MBP, and histones from CSF and sera was also demonstrated using their isoelectrofocusing. The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10.

scholarly journals Hydrolysis of myelin basic protein by polyclonal catalytic IgGs from the sera of patients with multiple sclerosis

2004 ◽  
Vol 8 (3) ◽  
pp. 359-368 ◽  
Author(s):  
Darya I. Polosukhina ◽  
Tatyana G. Kanyshkova ◽  
Boris M. Doronin ◽  
Olga B. Tyshkevich ◽  
Valentina N. Buneva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Hydrolysis Of

Metal-dependent hydrolysis of myelin basic protein by IgGs from the sera of patients with multiple sclerosis

2006 ◽  
Vol 103 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Dar’ya I. Polosukhina ◽  
Tat’yana G. Kanyshkova ◽  
Boris M. Doronin ◽  
Olga B. Tyshkevich ◽  
Valentina N. Buneva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Hydrolysis Of

Site-specific degradation of myelin basic protein by the proteasome

2009 ◽  
Vol 425 (1) ◽  
pp. 68-72 ◽  
Author(s):  
A. A. Belogurov ◽  
N. A. Ponomarenko ◽  
V. M. Govorun ◽  
A. G. Gabibov ◽  
A. V. Bacheva
Keyword(s):  
Myelin Basic Protein ◽  
Basic Protein ◽  
Site Specific ◽  
Specific Degradation

scholarly journals IgGs-Abzymes from the Sera of Patients with Multiple Sclerosis Recognize and Hydrolyze miRNAs

2021 ◽  
Vol 22 (6) ◽  
pp. 2812
Author(s):  
Evgeny A. Ermakov ◽  
Evelina M. Kabirova ◽  
Valentina N. Buneva ◽  
Georgy A. Nevinsky
Keyword(s):  
Multiple Sclerosis ◽  
Basic Protein ◽  
Intrinsic Property ◽  
Relative Activity ◽  
Igg Antibodies ◽  
Site Specific ◽  
Secondary Progressive ◽  
Healthy Donors ◽  
Relapsing Remitting ◽  
Hydrolysis Of

Autoantibodies-abzymes hydrolyzing DNA, myelin basic protein, and oligosaccharides have been revealed in the sera of patients with multiple sclerosis (MS). In MS, specific microRNAs are found in blood and cerebrospinal fluid, which are characterized by increased expression. Autoantibodies, specifically hydrolyzing four different miRNAs, were first detected in the blood of schizophrenia patients. Here, we present the first evidence that 23 IgG antibodies of MS patients effectively recognize and hydrolyze four neuroregulatory miRNAs (miR-137, miR-9-5p, miR-219-2-3p, and miR-219-5p) and four immunoregulatory miRNAs (miR-21-3p, miR-146a-3p, miR-155-5p, and miR-326). Several known criteria were checked to show that the recognition and hydrolysis of miRNAs is an intrinsic property of MS IgGs. The hydrolysis of all miRNAs is mostly site-specific. The major and moderate sites of the hydrolysis of each miRNA for most of the IgG preparations coincided; however, some of them showed other specific sites of splitting. Several individual IgGs hydrolyzed some miRNAs almost nonspecifically at nearly all internucleoside bonds or demonstrated a combination of site-specific and nonspecific splitting. Maximum average relative activity (RA) was observed in the hydrolysis of miR-155-5p for IgGs of patients of two types of MS—clinically isolated syndrome and relapsing-remitting MS—but was also high for patients with primary progressive and secondary progressive MS. Differences between RAs of IgGs of four groups of MS patients and healthy donors were statistically significant (p < 0.015). There was a tendency of decreasing efficiency of hydrolysis of all eight miRNAs during remission compared with the exacerbation of the disease.

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