Autoantibodies and Natural Catalytic Antibodies in Health, Multiple Sclerosis, and Some Other Diseases

Nevinsky, Georgy A.; Buneva, Valentina N.

doi:10.3233/nib-2012-012042

Cited by 33 publications

(252 citation statements)

References 95 publications

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“…Artificial abzymes are abzymes against analogs of transition states of catalytic reactions [3][4][5][6][7] or antiidiotypic Abs induced by a primary antigen, which may show some of its features including the catalytic activity (for review also see [8][9][10][11][12]). During past two decades it has become clear that auto-antibodies (auto-Abs) from the sera of patients with different autoimmune diseases can possess enzymatic activities and that their occurrence is a distinctive feature of autoimmune diseases (reviewed in [13][14][15][16][17]). It is thought that abzymes may play a significant role in forming specific pathogenic patterns and clinical settings in different autoimmune conditions through their broadened auto-Ab properties [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…During past two decades it has become clear that auto-antibodies (auto-Abs) from the sera of patients with different autoimmune diseases can possess enzymatic activities and that their occurrence is a distinctive feature of autoimmune diseases (reviewed in [13][14][15][16][17]). It is thought that abzymes may play a significant role in forming specific pathogenic patterns and clinical settings in different autoimmune conditions through their broadened auto-Ab properties [13][14][15][16][17]. Patients with autoimmune diseases produce Abs to nucleoprotein complexes, to DNA and to enzymes that participate in nucleic acid metabolism [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…It is thought that abzymes may play a significant role in forming specific pathogenic patterns and clinical settings in different autoimmune conditions through their broadened auto-Ab properties [13][14][15][16][17]. Patients with autoimmune diseases produce Abs to nucleoprotein complexes, to DNA and to enzymes that participate in nucleic acid metabolism [13][14][15][16][17]. In autoimmune diseases, there can be a spontaneous induction of anti-idiotypic antibodies, which are Abs elicited by a primary antigen, including some with catalytic activity, or transition from polyreactive catalytic activity to autoantigen-directed activity.…”

Section: Introductionmentioning

confidence: 99%

“…In autoimmune diseases, there can be a spontaneous induction of anti-idiotypic antibodies, which are Abs elicited by a primary antigen, including some with catalytic activity, or transition from polyreactive catalytic activity to autoantigen-directed activity. Natural abzymes hydrolyzing DNA, RNA, polysaccharides, oligopeptides, and proteins are present in the serum of patients with several autoimmune and viral diseases (reviewed in [13][14][15][16][17]). Healthy humans do not develop abzymes with detectable DNase and RNase activities, their levels being usually on the borderline of sensitivity of the detection methods [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…It has recently been shown that myelin basic protein (MBP)hydrolyzing activity is an intrinsic property of IgGs, IgMs, and IgAs from the sera of MS patients [17][18][19][20][21][22]. Recognition and degradation of MBP peptides by serum auto-Abs were confirmed as a novel biomarker for MS [21][22].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

et al. 2014

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It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

et al. 2014

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Systemic lupus erythematosus: molecular cloning of several recombinant DNase monoclonal kappa light chains with different catalytic properties

Botvinovskaya

Kostrikina

Buneva

et al. 2013

J of Molecular Recognition

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An immunoglobulin light chain phagemid library derived from peripheral blood lymphocytes of three patients with systemic lupus erythematosus was used. Phage particles displaying DNA binding light chains were isolated by affinity chromatography on DNA-cellulose, and the fraction eluted by an acidic buffer (pH 2.6) was used for preparation of individual monoclonal light chains (MLChs, 28 kDa). Thirty three of 687 individual colonies obtained were randomly chosen for study of MLCh DNase activity. Nineteen of 33 clones contained MLChs with DNase activity. Four preparations of MLChs were expressed in Escherichia coli in soluble form, purified by metal chelating chromatography followed by gel filtration, and studied in detail. Detection of DNase activity after SDS-PAGE in a gel containing DNA demonstrated that the four MLChs are not contaminated by canonical DNases. The MLChs demonstrated one or two pH optima. They were inactive after the dialysis against ethylenediaminetetraacetic acid but could be activated by several externally added metal ions; the ratio of relative activity in the presence of Mg(2+) , Mn(2+) , Ni(2+) , Ca(2+) , Zn(2+) , and Co(2+) was individual for each MLCh preparation. K(+) and Na(+) inhibited the DNase activity of various MLChs at different concentrations. Hydrolysis of DNA by all four MLCh was saturable and consistent with Michaelis-Menten kinetics. These clones are the first examples of recombinant MLChs possessing high affinity for DNA (Km = 3-9 nM) and demonstrating high kcat values (3.4-6.9 min(-1) ). These observations suggest that the systemic lupus erythematosus light chain repertoire can serve as a source of new types of DNases.

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Why specific anti-integrase antibodies from HIV-infected patients can efficiently hydrolyze 21-mer oligopeptide corresponding to antigenic determinant of human myelin basic protein

et al. 2013

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Human immunodeficiency virus-infected patients possess anti-integrase (IN) catalytic IgGs and IgMs (abzymes), which, unlike canonical proteases, specifically hydrolyze only intact globular IN. Anti-myelin MBP abzymes from patients with multiple sclerosis and systemic lupus erythematosus efficiently hydrolyze only intact MBP. Anti-MBP and anti-IN abzymes do not hydrolyze several other tested control globular proteins. Here, we show that anti-IN abzymes efficiently hydrolyze a 21-mer oligopeptide (OP21) corresponding to one antigenic determinant (AGD) of MBP, whereas anti-MBP abzymes extremely poorly cleave oligopeptides corresponding to AGDs of IN. All sites of IgG-mediated and IgM-mediated proteolysis of OP21 by anti-IN abzymes were found for the first time by a combination of reverse phase and thin layer chromatography and mass spectrometry. Several clustered sites of OP21 cleavage were revealed and compared with the cleavage sites within the complete IN. Several fragments of OP21 had good homology with many fragments of the IN sequence. The active sites of anti-IN abzymes are known to be located on their light chains, whereas heavy chains are responsible for the affinity for protein substrates. Interactions of intact IN with both light and heavy chains of the abzymes provide high affinity for IN and the specificity of its hydrolysis. Our data suggest that OP21 interacts mainly with the light chains of polyclonal anti-IN abzymes, which possess lower affinity and specificity for substrate. The hydrolysis of the non-cognate OP21 oligopeptide may be also less specific than the hydrolysis of the globular IN because in contrast to previously described serine protease-like abzymes against different proteins, anti-IN abzymes possess serine, thiol, acidic, and metal-dependent protease activities.

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Autoantibodies and Natural Catalytic Antibodies in Health, Multiple Sclerosis, and Some Other Diseases

Cited by 33 publications

References 95 publications

Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

Systemic lupus erythematosus: molecular cloning of several recombinant DNase monoclonal kappa light chains with different catalytic properties

Why specific anti-integrase antibodies from HIV-infected patients can efficiently hydrolyze 21-mer oligopeptide corresponding to antigenic determinant of human myelin basic protein

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