Natural Catalytic Antibodies in Norm and in HIV-Infected Patients

Nevinsky, Georgy A.

doi:10.5772/22294

Cited by 6 publications

(20 citation statements)

References 120 publications

(193 reference statements)

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“…The catalysis mediated by artificial abzymes is usually characterized by relatively lower reaction rates than for canonical enzymes [3][4][5][6]34]. The known k cat values for natural abzymes from autoimmune patients catalyzing many different chemical reactions vary in the range of 1 × 10 [3][4][5][6]34]. At the same time, the catalytic centers of abzymes, including proteolytic ones, are usually located on the light chain, while the heavy chain is mainly responsible for the specific antigen recognition and the increased antigen affinity for abzymes.…”

Section: Discussionmentioning

confidence: 99%

“…Many pro-and eukaryotic DNases including human DNase I (h-DNase I) [40,41] as well as DNase abzymes from the sera of patients with different pathologies [3][4][5][6]34] are Me 2+ -dependent, while other DNases including DNase II and some subfractions of DNase sIgAs from human milk are Me 2+ -independent. Therefore, we have analyzed the relative activities (RAs) of the MLCh before and after its dialysis against EDTA; after dialysis the MLCh completely lost the activity, but recovered DNase activity after addition of different external metal ions ( Figure 6C).…”

Section: Dependence Of Mlch Dnase Activity On Different Metal Ionsmentioning

confidence: 99%

“…The pH optima for various canonical DNases are very different, but each of them usually demonstrates only one pH optimum [40,41]. In contrast to all canonical DNases, pool of polyclonal DNase Abs from the sera patients with different diseases can contain from one to many monoclonal abzymes; some preparations can demonstrate from one to 2-8 pronounced optima at pH range from 5 to 10 [3][4][5][6]34]. We have analyzed pH optimum for the MLCh-25 in the presence of 5 mM MnCl 2 and 30 mM NaCl.…”

Section: Ph Optimum Of Dnase Activity Of Mlchmentioning

confidence: 99%

“…Several monoclonal mouse SLE IgGs against B-DNA of different sequences efficiently hydrolyze single-and double-stranded DNA and RNA in a sequence-independent manner, with the hydrolysis of RNA being 30-100-fold faster than of DNA [20]. In addition, immunization of rabbits with DNA, RNA, DNase I, DNase II, and pancreatic RNase A produced IgGs with intrinsic DNase and RNase activities ( [34] and references therein). It was shown that small fractions of the preparations of total polyclonal IgGs against DNase I, DNase II, and RNase demonstrate high DNase and RNase activities belong to antiidiotypic Abs to these enzymes, but they also contain small fractions interacting no with Sepharose bearing Abs against these enzymes, but interact with nucleic acids bound to these enzymes [34].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, immunization of rabbits with DNA, RNA, DNase I, DNase II, and pancreatic RNase A produced IgGs with intrinsic DNase and RNase activities ( [34] and references therein). It was shown that small fractions of the preparations of total polyclonal IgGs against DNase I, DNase II, and RNase demonstrate high DNase and RNase activities belong to antiidiotypic Abs to these enzymes, but they also contain small fractions interacting no with Sepharose bearing Abs against these enzymes, but interact with nucleic acids bound to these enzymes [34]. It means that these Abs are against nucleic acids bound with the enzymes used.…”

Section: Introductionmentioning

confidence: 99%

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SLE: Unusual Recombinant Monoclonal Light Chain NGTA3-Pro-DNase Possessing Three Different Activities Trypsin-like, Metalloprotease and DNase

Timofeeva¹,

Buneva²,

Nevinsky³

2017

Lupus Open Access

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Objective: DNA-and myelin basic protein (MBP)-hydrolyzing antibodies can play an important role in the pathogenesis of systemic lupus erythematosus (SLE), therefore their analysis seems to be important. Results:In mammalians there are serine proteases, metalloproteases, and DNases. Each of these and many other enzymes catalyze only one chemical reaction. Very unusual and unpredictable situation was revealed by us in the case of monoclonal abzymes corresponding to the sera of patients with SLE. The small pools of phage particles displaying light chains with different affinity for myelin basic protein (MBP) were isolated by affinity chromatography on MBP-Sepharose. In contrast to canonical enzymes, one of twenty five MLChs demonstrated three different enzymatic activities; it efficiently hydrolyzed MBP (but not other proteins) and DNA. Other twenty four MLChs hydrolyzed only MBP. The proteolytic activity of NGTA3-pro-DNase was efficiently inhibited by specific inhibitors of serine-like (PMSF) and metalloproteases (EDTA). Protease and DNase properties of NGTA3-pro-DNase differ significantly from those for the corresponding canonical enzymes.Conclusion: This is the first example of monoclonal antibodies with three different catalytic activities. The principal possibility of the existence of monoclonal antibodies with several different enzymatic activities is unexpected but very important for the further understanding of unknown biological functions of human immunoglobulins.

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Section: Discussionmentioning

confidence: 99%

Section: Dependence Of Mlch Dnase Activity On Different Metal Ionsmentioning

confidence: 99%

Section: Ph Optimum Of Dnase Activity Of Mlchmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SLE: Unusual Recombinant Monoclonal Light Chain NGTA3-Pro-DNase Possessing Three Different Activities Trypsin-like, Metalloprotease and DNase

Timofeeva¹,

Buneva²,

Nevinsky³

2017

Lupus Open Access

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Effect of Myelin Oligodendrocyte Glycoprotein (MOG35-55) on Cell Differentiation and Abzymes Production in Transgenic EAE-Prone Th Mice with T Cells Response During the Development of Experimental Encephalomyelitis

Aulova

Urusov

Toporkova

et al. 2021

Preprint

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Background: The mechanisms of multiple sclerosis development are still unknown. It was shown that the development of experimental autoimmune encephalomyelitis (EAE) in EAE prone C57BL/6 mice (model mimicking human multiple sclerosis) having B and T lymphocyte responses is associated with modification in the differentiation profiles of bone marrow hematopoietic stem cells (HSCs) and the increase in lymphocyte proliferation. Methods: Only T cell responses characterize other EAE transgenic prone Th mice. Different characteristics of the autoimmune reaction in Th mice were analyzed. During the development of EAE (and inflammation processes), the differentiation profiles of Th mice bone marrow HSCs (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T, and B lymphocytes) were noticeably or significantly different in male and female mice before and after their immunization with myelin oligodendrocyte glycoprotein (MOG35-55). Results: The patterns of B and T (including CD4 and CD8 cells) lymphocytes proliferation in several organs (spleen, thymus, bone marrow, blood, and lymph nodes) during spontaneous (completely untreated mice) and MOG-treatment-accelerated development of EAE was also remarkably or significantly different in male and female mice. All these changes in male and female mice, despite some differences, were coupled with the increase in the concentrations of autoantibodies against DNA, myelin basic protein, and MOG, and with the increase in the relative activity of catalytic antibodies hydrolyzing these antigens. Conclusions: A comparison of the changes in a large number of parameters characterizing the development of EAE in Th and C57BL/6 mice was carried out. It was shown that MOG very much accelerates the development of EAE in Th mice with T cell responses. Despite some differences, the general patterns of the developing of spontaneous and MOG-accelerated EAE in Th male and female mice and in C57BL/6 mice are similar to a notable extent.

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Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States

Ermakov

Nevinsky

Buneva

2020

IJMS

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Immunoglobulins are known to combine various effector mechanisms of the adaptive and the innate immune system. Classical immunoglobulin functions are associated with antigen recognition and the initiation of innate immune responses. However, in addition to classical functions, antibodies exhibit a variety of non-canonical functions related to the destruction of various pathogens due to catalytic activity and cofactor effects, the action of antibodies as agonists/antagonists of various receptors, the control of bacterial diversity of the intestine, etc. Canonical and non-canonical functions reflect the extreme human antibody repertoire and the variety of antibody types generated in the organism: antigen-specific, natural, polyreactive, broadly neutralizing, homophilic, bispecific and catalytic. The therapeutic effects of intravenous immunoglobulins (IVIg) are associated with both the canonical and non-canonical functions of antibodies. In this review, catalytic antibodies will be considered in more detail, since their formation is associated with inflammatory and autoimmune diseases. We will systematically summarize the diversity of catalytic antibodies in normal and pathological conditions. Translational perspectives of knowledge about natural antibodies for IVIg therapy will be also discussed.

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Natural Catalytic Antibodies in Norm and in HIV-Infected Patients

Cited by 6 publications

References 120 publications

SLE: Unusual Recombinant Monoclonal Light Chain NGTA3-Pro-DNase Possessing Three Different Activities Trypsin-like, Metalloprotease and DNase

SLE: Unusual Recombinant Monoclonal Light Chain NGTA3-Pro-DNase Possessing Three Different Activities Trypsin-like, Metalloprotease and DNase

Effect of Myelin Oligodendrocyte Glycoprotein (MOG35-55) on Cell Differentiation and Abzymes Production in Transgenic EAE-Prone Th Mice with T Cells Response During the Development of Experimental Encephalomyelitis

Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States

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