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A G Gabibov

Publications and source records attributed to A G Gabibov.

At least 19 recordsLinked to original sources
PubMed2006

[Catalytic autoantibodies as a new molecular instrument in rheumatological practice].

AIM: To compare clinicopathogenetic value of DNA-hydrolizing autoantibodies or DNA-abzymes in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). MATERIAL AND METHODS: We studied sera from 180 patients with SLE, 180 RA patients and 128 healthy donors matched by age and gender; assessed catalytic and cytotoxic activity of DNA-abzymes in patients with different variants of SLE and RA course. RESULTS: The highest catalytic and cytotoxic activities of DNA abzymes were observed in SLE patients. In SLE catalytic and cytotoxic activities of DNA abzymes ranged widely and their mean values depended on SLE activity in patients with systemic lesions. DNA-abzymes in RA patients showed lower catalytic and cytotoxic activities in relation to substrate DNA and target cells than in SLE. DNA-abzymes occurred most frequently in patients with high activity of RA, slow-progressive and lingering course of RA, especially in early development of visceral (extra-articular) pathology. Characteristic for DNA-abzymes in RA and SLE is the phenomenon of wide-range fluctuations due to factors determinating probability of induction of function of Ab-mediated catalysis and, therefore, incidence rates of DNA-abzymes, probably catalytic autoAb of the other specificity in a population of patients with systemic autoimmune diseases. CONCLUSION: The data indicate the validity of DNA abzymes use in clinical practice for realization of diagnostic and therapeutic programs in SLE and RA.

Adult↗
PubMed2005

[Catalytic autoantibodies in autoimmune myocarditis: clinical and pathogenetic implications].

AIM: To evaluate pathogenetic and clinical significance of autoantibodies (AAB) with catalytic activity in the serum of patients with autoimmune myocarditis (AM). MATERIAL AND METHODS: The study was made on the sera from 99 patients with AM of different course: malignant, benign, myocardiosclerosis (MCS). In addition to standard immunological parameters, the study was made of serum levels of anticardiomyosine-antiCM (protabzymes) and anti-DNA (DNA-abzymes) of AAB. After obtaining anti-CM and anti-DNA IgG-AT, we determined non-specific and specific proteolytic activity of anti-CM. RESULTS: Maximal specific activity of protabzymes was seen in 73% patients with malignant AM, it correlated with blood levels of anti-CM AAB, DNA-abzymes activity was very high in 45% patients. In MCS proteolytic activity of autoAT was absent in 61% patients. In benign AM occurrence of protabzymes was confirmed in 35% cases. Elevated DNA-hydrolyzing activity of DNA-abzymes occurred in 13% cases. The activity had no significant correlation with serum titers of AB. In MCS proteolytic activity of AAB was absent in 61% cases, but high activity of anti-CM AAB was in 28%. The activity of DNA-abzymes in 44% ranged considerably which, in seropositive cases, detected significant correlation with serum titers of DNA-binding autoAT. CONCLUSION: Evaluation of catalytic activity of AAB may be considered as a criterial test assessing the stage, clinical variants and severity of AM. It also permits formulation of the disease prognosis and its possible outcomes.

Antibodies, Catalytic↗
PubMed2005

[Introduction to medical abzymology: the present and the prospect].

The last decade of the 20th century was marked by appearance of a new field at the interfaces between modern immunology, biochemistry, molecular biology, and pathology. The name of this field, abzymology, descends from the terms "antibody" and "enzymes". The new direction is concerned with obtaining and study of abzymes, catalytic antibodies. This new class of biocatalyzers may be obtained artificially, by immunization of animals with transition state analogs, or by induction of anti-idiotypic antibodies to enzymes. By now, these approaches have allowed biocatalytic conversions of dosens of biochemical reactions using antibodies. Many of them do not have natural enzymatic "analogs". This have provided a real possibility to obtain "catalytic vaccines", moleculas of immunoglobulins, capable of destroying such harmful conpounds as pesticides, toxic agents, and narcotics. Abzymes may also be obtained from human and animal serum in various pathologic conditions. Nowadays it is obvious that the highest level of catalytic activity is observed in autoimmune conditions. Most likely, this aspect of abzymology may be considered from the point of view of prospects in diagnostics, as well as to be one of the aspects of studying abzymology.

Animals↗
PubMed2005

[DNA-abzymes in rheumatoid arthritis: pathogenetic and clinical significance].

AIM: To study possible pathogenetic role and clinical significance of DNA-hydrolysing autoantibodies (autoAB) or DNA-abzymes in patients with rheumatoid arthritis. MATERIAL AND METHODS: Prevalence of DNA-abzymes and their catalytic activity were studied in 400 patients with rheumatoid arthritis (RA) and 88 healthy donors matched by age and gender. RESULTS: Associated with DNA-binding autoAB DNA-hydrolysing activity was detected in 41.5% cases of RA. DNA-abzymes were maximally active in men with rheumatoid factor (RF) and women without RF, while it was minimal in men without RF and women with RF. By catalytic activity there was no significant differences between patients with RF and without it. The highest catalytic activity of DNA abzymes was detected in patients with distinct extraarticular pathology. DNA-abzymes were also active in patients with x-ray stage III-IV of the disease in association with high prevalence of catalytic autoAB. DNA abzymes were also active in patients with RA activity stage II and III. CONCLUSION: It is possible to use DNA-abzymes in clinical practice for monitoring of the disease activity in RA.

Antibodies, Catalytic↗
PubMed2002

Anti-DNA autoantibodies reveal toxicity to tumor cell lines.

Cytotoxicity of anti-DNA autoantibodies from sera of SLE and CLL patients was assayed on permanent cell lines L929, HL-60, Raji, and K562. L929 cells appeared to be the most sensitive to antibody treatment. DNA-hydrolyzing properties of the same autoantibody preparations were analyzed in parallel. The data obtained outlined the correlation between cytotoxicity and DNA-hydrolyzing properties of these autoantibodies. It was shown that treatment of the cells with cytotoxic anti-DNA autoantibodies induced internucleosomal DNA fragmentation and Annexin V binding to the cell surface characteristic of apoptotic pathway of cell death. A time-dependent profile of antibody-mediated toxicity to L929 cells suggested recruitment of at least two distinct mechanisms of cell death. The first peak of cell death observed in 3 h of incubation was completely inhibited by preincubation of cells with caspase inhibitor YVAD-CHO, while the second increase in cell mortality (18-30 h) persisted. Possible mechanisms for anti-DNA autoantibody cytotoxicity are discussed.

Antibodies, Antinuclear↗
PubMed2002

Antibody proteases: induction of catalytic response.

Most of the data accumulated throughout the years on investigation of catalytic antibodies indicate that their production increases on the background of autoimmune abnormalities. The different approaches to induction of catalytic response toward recombinant gp120 HIV-1 surface protein in mice with various autoimmune pathologies are described. The peptidylphosphonate conjugate containing structural part of gp120 molecule is used for reactive immunization of NZB/NZW F1, MRL, and SJL mice. The specific modification of heavy and light chains of mouse autoantibodies with Val-Ala-Glu-Glu-Glu-Val-PO(OPh)2 reactive peptide was demonstrated. Increased proteolytic activity of polyclonal antibodies in SJL mice encouraged us to investigate the production of antigen-specific catalytic antibodies on the background of induced experimental autoimmune encephalomyelitis (EAE). The immunization of autoimmune-prone mice with the engineered fusions containing the fragments of gp120 and encephalitogenic epitope of myelin basic protein (MBP(89-104)) was made. The proteolytic activity of polyclonal antibodies isolated from the sera of autoimmune mice immunized by the described antigen was shown. Specific immune response of SJL mice to these antigens was characterized. Polyclonal antibodies purified from sera of the immunized animals revealed proteolytic activity. The antiidiotypic approach to raise the specific proteolytic antibody as an "internal image" of protease is described. The "second order" monoclonal antibodies toward subtilisin Carlsberg revealed pronounced proteolytic activity.

Animals↗
PubMed2001

[DNA-abzymes and their clinical significance in systemic lupus erythematosis].

AIM: To evaluate occurrence of DNA-abzymes with catalytic (DNA-hydrolysing) and cytotoxic properties in patients with systemic lupus erythematosus (SLE) for examination of clinical value of DNA-abzymes in diagnosis of autoimmune syndrome and apoptosis level in different variants of immunopathology. MATERIAL AND METHODS: The study group consisted of patients with verified SLE diagnosis (n = 120). They were compared to 72 patients with rheumatoid arthritis (RA), 82 patients with scleroderma systematica (SS), 60 patients with discoid lupus erythematosus (DLE), 88 patients with focal scleroderma (FS) and 198 autoimmune uveitis (AU) patients. 128 donors served control. Catalytic and cytotoxic activity of DNA-abzymes were determined by methods of molecular biology and enzymology. All the patients were examined for blood levels of IgG, IgM and IgA, anti-DNA, anti-Sm and other IgG-autoantibodies, CIC titers, phagocyting activity, content of main D-cell subpopulations. Key immunoregulatory indices were also estimated. RESULTS: DNA-abzymes were detected more often in SLE and RA patients. In SLE, catalytic and cytotoxic activities of DNA-abzymes reached their maximum. There was a correlation with leading clinicoimmunological signs of SLE. The disease was most severe with apparent immunopathology in patients with maximal catalytic and cytotoxic activity of DNA-abzymes. With lowering cytotoxic activity of DNA-abzymes more patients demonstrate low SLE activity without severe organic lesions and alleviated symptoms of immunopathology. CONCLUSION: An important role of DNA-abzymes in pathogenesis of SLE is shown. They are also valuable tools in diagnosis of various clinicoimmunological variants of the disease.

Apoptosis↗
PubMed2000

Enzyme mimicry by the antiidiotypic antibody approach.

The concept of "internal image" of antiidiotypic antibodies has provided the basis for eliciting catalytic antibodies. A monoclonal IgM 9A8 that was obtained as an antiidiotype to AE-2 mAb, a known inhibitor of acetylcholinesterase, displayed esterolytic activity. Study of recombinant Fab fragments and separate light and heavy chains of 9A8 confirmed that the antibody variable domain encodes the catalytic function, whereas neither part of the primary sequence of the Fab exhibited homology with the enzyme. The specific modification of the 9A8 variable domain by an active site-directed covalent inhibitor revealed the presence of an active site Ser residue. A three-dimensional modeling suggests the existence of a functional catalytic dyad Ser-His. Comparison of active sites of 9A8 and 17E8 esterolytic abzyme raised against transition-state analog revealed structural similarity although both antibodies were elicited by two different approaches.

Amino Acid Sequence↗
PubMed1998

Novel functional activities of anti-DNA autoantibodies from sera of patients with lymphoproliferative and autoimmune diseases.

DNA-hydrolyzing activity of IgG autoantibodies from sera of patients with various types of lymphoproliferative diseases was investigated. The association of DNA-hydrolyzing activity with the antibody (Ab) fraction has been proved by newly developed affinity-capture assay. Study of abzyme incidence in blood tumors and systemic lupus erythematosis (SLE) revealed linkage of anti-DNA Ab catalysts to mature B-cell tumors, and increased probability of DNA-abzymes formation on the background of autoimmune manifestations. These data suggest possible similarity between mechanisms of abzyme formation in SLE and B-cell lymphomas. A new mechanism of formation of DNA-specific catalytic Abs has been proposed based on the increased crossreactivity of polyclonal DNA-abzymes to DNA-depleted nuclear matrix proteins. The possibility of the abzyme production as Ab to the energetically destabilized ground state of the antigen has been discussed. Preliminary results were obtained that indicate the complement-independent cytotoxicity of anti-DNA autoantibodies isolated from blood of patients with SLE and chronic lymphocytic leukemia.

Antibodies, Antinuclear↗
PubMed1998

[Design of constructions for the expression of proteolytic antibody light chain].

A new system for the expression of a catalytic light chain antibody to the vasoactive intestinal peptide is described. The system made possible the isolation the large amounts of a homogeneous protein without any additional peptide domains. The preparation obtained can be used in further experiments on light chain crystallization and in X-ray-structural analysis of its catalytic center.

Antibody Formation↗
PubMed1997

DNA hydrolysis by monoclonal anti-ssDNA autoantibody BV 04-01: origins of catalytic activity.

Monoclonal anti-DNA autoantibody BV 04-01 catalyzed hydrolysis of DNA in the presence of Mg2+ ions. DNA hydrolyzing activity was associated with BV 04-01 IgG, Fab, and SCA 04-01 proteins. Pronounced cleavage specificity for both ss and dsDNA was observed with efficient hydrolysis of the C-rich region of the oligonucleotide A7C7ATATAGCGCGT7 as well as preference for cleavage within CG-rich regions of double-stranded DNA. Data on specificity of ssDNA hydrolysis and kinetic data obtained from wild-type SCA 04-01 and two SCA 04-01 mutants (L32Phe and L27dHis) were used to model the catalytically active antibody site utilizing the previously resolved X-ray structure of (dT)3 liganded Fab 04-01. The resulting model suggested that BV 04-01 activates the target phosphodiester bond by induction of conformational strain. In addition, the antibody-DNA complex contained a potential Mg2+ ion coordination site composed of the L32Tyr and L27dHis amino acid side chains and a DNA 3'-phosphodiester group. Induction of strain and metal coordination could be constituents of a mechanism by which this antibody catalyzed DNA hydrolysis. Sequence data for BV 04-01 VH and VL genes suggested that the proposed catalytic antibody active site was germ-line encoded. This observation suggests the hypothesis that catalytic activity might represent an important but unspecified function of some antibody molecules.

Animals↗