Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

Doronin, Vasilii B.; Parkhomenko, T. A.; Castellazzi, Massimiliano; Cesnik, Carlos E. S.; Buneva, Valentina N.; Granieri, Enrico; Nevinsky, Georgy A.

doi:10.1371/journal.pone.0154688

Cited by 25 publications

(60 citation statements)

References 47 publications

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“…As demonstrated before, the method of isolation of IgGs developed by us excludes contamination with classical enzymes . Based on several very strict criteria developed previously, we have reliably proven that DNase‐, MOG‐, MBP‐hydrolysing activities are intrinsic properties of IgG abzymes from the plasma of spontaneously diseased MOG and DNA‐met‐BSA treated C57BL/6 mice, and they are not because of co‐purified canonical DNases or proteases .…”

Section: Resultsmentioning

confidence: 60%

“…To protect Abs from viral and bacterial contamination, they were filtered through syringe‐driven filter units (Millex; 0.1 μm) and kept in sterilized tubes. The absence of viral and bacterial colonies in Ab preparations was checked as shown previously . SDS‐PAGE analysis proving electrophoretic homogeneity of IgGs under non‐reducing conditions (0.1%) was performed in 4‐15% gradient gels.…”

Section: Methodsmentioning

confidence: 99%

“…Current data demonstrate the appearance of myelin basic protein (MBP)‐ and DNA‐hydrolysing abzymes in the blood of patients with MS, SLE and several other AIDs . IgGs from the CSF of MS patients, which hydrolyse MBP, DNA and polysaccharides, are on average 30‐ to 60‐fold higher than those taken from the sera of the same patients . In AIDs, abzymes hydrolysing MBP can attack the protein of the myelin‐proteolipid sheath of axons and can play a harmful role in MS, SLE and other disease pathogenesis .…”

Section: Introductionmentioning

confidence: 99%

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Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes

Aulova

Toporkova

Lopatnikova

et al. 2018

J Cellular Molecular Medi

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252

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Experimental autoimmune encephalomyelitis (EAE)‐prone C57BL/6 mice are used as a model of human multiple sclerosis. We immunize mice with myelin oligodendrocyte glycoprotein (MOG), DNA–histone and DNA‐methylated bovine serum albumin (met‐BSA) complexes to reveal different characteristics of EAE development including bone marrow lymphocyte proliferation and differentiation profiles of hematopoietic stem cells. Immunization of C57BL/6 mice with MOG35‐55 results in the acceleration of EAE development. Anti‐DNA antibodies are usually directed against DNA–histone complexes resulting from cell apoptosis. During the acute EAE phase (7‐20 days after immunization), catalytic antibodies efficiently hydrolysing myelin basic protein (MBP), MOG and DNA are produced with parallel suppression of antibodies hydrolysing histones. We could show that in contrast to MOG, immunization with histone‐DNA results in a reduction of proteinuria, a significant increase in anti‐DNA, anti‐MBP and anti‐MOG antibody titres, as well as an increase in their catalytic activities for antigen hydrolysis, but slightly changes the concentration of cytokines. Contrary to MOG, DNA–histone and DNA‐met‐BSA only stimulated the formation of anti‐DNA antibodies hydrolysing DNA with a long delay (15‐20 days after immunization). Our data indicate that for C57BL/6 mice immunization with DNA‐met‐BSA and DNA–histone complexes may have opposing effects compared to MOG. DNA–histone stimulates the appearance of histone‐hydrolysing abzymes in the acute EAE phase, while abzymes with DNase activity appear at significantly later time‐points. We conclude that MOG, DNA–histone and DNA‐met‐BSA have different effects on numerous bone marrow, cellular, immunological and biochemical parameters of immunized mice, but all antigens finally significantly stimulate the development of the EAE.

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Section: Resultsmentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes

Aulova

Toporkova

Lopatnikova

et al. 2018

J Cellular Molecular Medi

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252

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show abstract

“…It was shown that IgGs from sera and cerebrospinal fluid of MS patients are active in the hydrolysis of DNA, MBP, and oligosaccharides. In addition, the specific RAs of these abzymes from the CSF of MS patients are dependently on their different activities were approximately 30-to 60-fold higher comparing to serum Abzs from the same patients [67][68][69]. It means that during spontaneous or induced development of ADs as a result of specific differentiation of lymphocytes in cerebrospinal fluid there may be formation of cells producing different catalytic antibodies directly in cerebrospinal fluid.…”

Section: Lymphocyte Proliferation In Sle Prone Micementioning

confidence: 92%

“…In this regard, data comparing relative Abz activities from serum and cerebrospinal fluid (CSF) of the same MS patients with multiple sclerosis should be noted [67][68][69]. It was shown that IgGs from sera and cerebrospinal fluid of MS patients are active in the hydrolysis of DNA, MBP, and oligosaccharides.…”

Section: Lymphocyte Proliferation In Sle Prone Micementioning

confidence: 99%

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Nevinsky¹

2017

Lupus

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321

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Systemic lupus erythematosus (SLE) is known as a systemic polyethiologic diffuse autoimmune disease characterized by connective tissue disorganization and the paramount damage of skin and visceral capillaries. Usually, SLE symptoms include high fever, hair loss, mouth ulcers, chest pain, swollen lymph nodes, painful and swollen joints, increased fatigue, and appearance of red rash more often on the face. The exact reason of SLE appearance is not really clear. Detection of catalytic Abs (abzymes) was shown to be the earliest indicator of different AI disease development. Some abzymes are cytotoxic and can play a dangerous negative role in the pathogenesis of AI diseases. SLE is characterized by the appearance of abzymes with several different catalytic functions including hydrolysis of peptides and proteins, DNA, RNA, and oligosaccharides. In addition, monoclonal SLE abzymes are characterized by extraordinary diversity in the affinity to the substrates, physicochemical and catalytic characteristics, optimal conditions of catalysis, cytotoxicity, etc. Production of abzymes in SLE mice is associated with changes in the differentiation of hematopoietic stem cells of bone marrow, increase in lymphocyte proliferation, and significant suppression of cell apoptosis in different organs. In this chapter, abzymes with different catalytic activities in SLE are described.

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Substrate specificity of IgGs with peroxidase and oxidoreductase activities from sera of patients with systemic lupus erythematosus and multiple sclerosis

Tolmacheva

Buneva

Nevinsky

2019

J of Molecular Recognition

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The analysis of IgGs to protect humans from oxidative stress through oxidation of harmful compounds was carried out. We have compared here for the first time peroxidase (in the presence of H 2 O 2 ) and oxidoreductase (in the absence of H 2 O 2 ) activities of IgGs from sera of healthy humans and patients with systemic lupus erythematosus (SLE) and multiple sclerosis (MS). In addition, substrate specificity of SLE and MS IgG preparations in the oxidation of different compounds was analyzed: 2,2′azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 3,3′-diaminobenzidine (DAB), homovanillic acid (HVA), o-phenylenediamine (OPD), α-naphthol, 3-amino-9ethylcarbazole (AEC), p-hydroquinone (pHQ), and adrenaline. IgGs of healthy humans and SLE and MS patients oxidized DAB, ABTS, and OPD due to their peroxidase and oxidoreductase activities, while other compounds were substrates of IgGs only in the presence of H 2 O 2 : adrenaline was not oxidized by both activities of IgGs. The average SLE IgGs peroxidase activity increased statistically significant in comparison with abzymes from healthy humans in the order (-fold): OPD (1.2) < DAB (1.7) < α-naphtol (2.2) ≤ AEC (2.4) < ABTS (4.5) < 5-ASA (10.6), while with oxidoreductase activity: OPD (1.8) ≤ DAB (2.1-fold) < ABTS (5.0). Only HVA was oxidized by IgGs with peroxidase activity of healthy donors faster than by SLE (1.3-fold) and MS abzymes (2.4-fold). In the oxidation of several substrates, only three IgGs of MS patients were used. The data speak of a tendency to increase the peroxidase and oxidoreductase activities of MS IgGs in comparison with healthy donors, but to a lesser extent: OPD (1.1 to 1.2-fold) ≤ ABTS (1.2 to 1.8-fold). It was shown that development of SLE and MS leads to increase in peroxidase and oxidoreductase activities of IgGs toward most of classical substrates. Thus, abzymes can serve as an additional factor of reactive oxygen species detoxification protecting of patients with SLE and MS from some harmful compounds somewhat better than healthy peoples.

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Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

Cited by 25 publications

References 47 publications

Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes

Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Substrate specificity of IgGs with peroxidase and oxidoreductase activities from sera of patients with systemic lupus erythematosus and multiple sclerosis

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