Immunization of rabbits with DNase I produces polyclonal antibodies with DNase and RNase activities

Krasnorutskii, Michael A.; Buneva, Valentina N.; Nevinsky, Georgy A.

doi:10.1002/jmr.890

Cited by 18 publications

(34 citation statements)

References 36 publications

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“…Interestingly, when Abs were eluted from DNA-cellulose by a NaCl gradient (0-3 M) and then acidic buffer (pH 2.6) the Abs and their DNase and RNase activities were distributed all over the chromatography profile (for example, Figure 8A) [70,71]. The same situation was observed for Abs with nuclease activities from sera of MS patients [8,[80][81][82], and rabbits immunized with DNA, RNA, DNase I, DNase II, and pancreatic RNase [49,50,[55][56][57]. The affinity of Abs fractions for these substrates was increased gradually with the increase in eluting salts concentrations.…”

Section: Polyclonal Dnase and Rnase Abzymesmentioning

confidence: 67%

“…Our findings indicate that a variety of anti-DNA and anti-RNA abzymes are able to hydrolyze both DNA and RNA [13][14][15][16][17][18][19][20][21][22]. In this respect, it should be mentioned that after immunization of rabbits with DNA, RNA, DNase I, DNase II, and pancreatic RNase I, antinuclease IgGs with different affinity to DNA were separated for several fractions by chromatography on DNA-cellulose [49,50,[55][56][57].…”

Section: Polyclonal Dnase and Rnase Abzymesmentioning

confidence: 91%

“…It was shown that 150 kDa SLE IgGs are electrophoretically homogeneous and in contrast to Abs from healthy donors are active in the hydrolysis of MBP [55,77]. To prove that MBP-hydrolyzing activity of SLE IgGs is their intrinsic property, we have checked the fulfilment of several known strict criteria described above including analysis of Ab protease activity after SDS-PAGE (Figure 7) [77].…”

Section: Lupus 70mentioning

confidence: 99%

“…We have suggested that polyclonal DNase Abzs in autoimmune patients may be a cocktail of abzymes against complexes of proteins with DNA and RNA and antiidiotypic abzymes to different DNA-hydrolyzing enzymes. Therefore, we have immunized rabbits with DNase II, DNase I, pancreatic RNase A, DNA, and RNA [49,50,[55][56][57]. In all cases, abzymes with intrinsic DNase and RNase activities were revealed.…”

Section: Introductionmentioning

confidence: 99%

“…In all cases, abzymes with intrinsic DNase and RNase activities were revealed. IgGs against DNase I with DNase activity also have an antiidiotypic nature [55]. Interestingly, 74-85% of the total polyclonal IgGs against RNase A possessing RNase and DNase activities belong to antiidiotypic Abs, while 15-26% of the Abzs cannot interact with affinity sorbent-bearing Abs against RNase A; they bind with DNA-and RNA-Sepharoses and may be antibodies to nucleic acids bound to RNase [56].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Polyclonal Dnase and Rnase Abzymesmentioning

confidence: 67%

Section: Polyclonal Dnase and Rnase Abzymesmentioning

confidence: 91%

Section: Lupus 70mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Nevinsky¹

2017

Lupus

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321

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Diversity of DNA‐hydrolyzing antibodies from the sera of autoimmune‐prone MRL/MpJ‐lpr mice

Kostrikina

Kolesova

Orlovskaya³

et al. 2010

J of Molecular Recognition

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It has been shown for the first time that polyclonal IgG abzymes (Abzs) with DNase activity from the sera of autoimmune-prone MRL/MpJ-lpr mice can be separated by isoelectric focusing into many subfractions having the isoelectric points (pI) from 4.5 to 9, with the maximal activity for Abzs with pI = 6.5-9.0. Affinity chromatography on DNA-cellulose separated DNase IgGs into many subfractions demonstrating a range of affinities for DNA and different levels of the relative DNase activities (RDA) due to intrinsically bound metals and after addition of external Mg(2+) , Mn(2+) , Ca(2+), and Mg(2+) +Ca(2+). Some fractions significantly increase RDAs in the presence of external ions (Mg(2+) + Ca(2+) > Mg(2+) > Mn(2+) > Ca(2+)), while each of this cofactor can also inhibit or have no influence on the RDAs of another fractions. It is known that complexes of DNA with histones and other proteins of apoptotic cells are the primary immunogens in systemic lupus erythematosus (SLE). Bovine serum albumin (BSA) and methylated BSA (mBSA) increase the RDAs of only some fractions, while have no effect or inhibit other IgG fractions. The ratio of the RDAs in the presence of all metal ions, BSA, and mBSA was individual for every abzyme fraction. Mn(2+) and Ca(2+) stimulated accumulation of only relaxed form of supercoiled DNA (scDNA) in the case of all subfractions, while in the presence of Mg(2+) antibodies (Abs) of some subfractions (and in the presence of Mn(2+) +Ca(2+) all subfractions) produced relaxed DNA (rDNA) and linear DNA (linDNA) in a variable extent. The data obtained show that the polyclonal Abzs of mice may be a cocktail of Abs directly to DNA, RNA, and their complexes with proteins and anti-idiotypic Abs to active centers of different nucleases. The diversity of the physicochemical and kinetic characteristics of the Abzs seems to be significantly widened when pre-diseased mice spontaneously develop the disease.

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IgGs containing λ‐ and κ‐type light chains and of all subclasses (IgG1–IgG4) from the sera of patients with autoimmune diseases and viral and bacterial infections hydrolyze DNA

Parkhomenko

Buneva

Доронин

et al. 2012

J of Molecular Recognition

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We present the first evidence demonstrating that small fractions of IgGs of all four subclasses (IgG1-IgG4) from patients with viral (tick-borne encephalitis), bacterial infections (streptococcal infection or erysipelas), and suppurative surgical infections caused by epidermal staphylococci as well as from patients with autoimmune diseases (systemic lupus erythematosus and multiple sclerosis) are catalytically active in the hydrolysis of supercoiled DNA. The hydrolysis of DNA was analyzed by agarose gel electrophoresis. The catalytic activities of nonfractionated IgGs increased in the following order: tick-borne encephalitis < suppurative surgical infection < streptococcal infection < multiple sclerosis < systemic lupus erythematosus, whereas IgGs of healthy donors were inactive. However, the pools of antibodies corresponding to any particular disease were characterized by a specific ratio of IgGs of all four subclasses (IgG1-IgG4) and IgGs containing λ- and κ-type light chains, and each of these subfractions of immunoglobulins demonstrated characteristic relative DNase activity. The relative activities of IgGs containing λ-type light chains may on average be higher, lower, or comparable with those for IgGs with κ-type light chains. The relative contributions of IgGs of different subclasses to the total activity of IgGs also varied widely in the case of various diseases: IgG1 (7%-45%), IgG2 (0.4%-73%), IgG3 (0%-12%), and IgG4 (9%-66%). Thus, immune systems of patients with different diseases can generate a variety of anti-DNA abzymes of different types and with different catalytic properties, which can play an important role in the pathogenesis or protection from the development of these diseases.

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Immunization of rabbits with DNase I produces polyclonal antibodies with DNase and RNase activities

Cited by 18 publications

References 36 publications

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Diversity of DNA‐hydrolyzing antibodies from the sera of autoimmune‐prone MRL/MpJ‐lpr mice

IgGs containing λ‐ and κ‐type light chains and of all subclasses (IgG1–IgG4) from the sera of patients with autoimmune diseases and viral and bacterial infections hydrolyze DNA

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