Special Features of the DNA-Hydrolyzing Activity of the Antibodies in Systemic Lupus Erythematosus

Abstract

Two types of IgG anti-DNA antibodies exhibiting DNA-hydrolyzing activity have been isolated from blood serum of patients with systemic lupus erythematosus. This DNase activity of antibodies differs from serum DNases by the non-processive mode, temperature resistance, pH optimum, and the rate of DNA hydrolysis. It is suggested that the anti-DNA antibody molecule possessing DNase activity contains two sites: one site determines specificity of antibody-DNA interaction, whereas the other is responsible for manifestation of the catalytic activity.

Virus-induced preferential antibody gene-usage and its importance in humoral autoimmunity

“…activity are also called "abzyme". Abzymes are able to enter cell nucleus, bind and cleave DNA probably using their heavy chains (HCs) to bind the DNA and their light chains (LCs) to destroy dsDNA [94]. The DNA disruption can stop cell life cycle perturbing the protein pathways and triggering programmed cell death [94].…”

“…Abzymes are able to enter cell nucleus, bind and cleave DNA probably using their heavy chains (HCs) to bind the DNA and their light chains (LCs) to destroy dsDNA [94]. The DNA disruption can stop cell life cycle perturbing the protein pathways and triggering programmed cell death [94]. In turn, abzyme-mediated cell disruption leads to the release of cellular and nuclear contents sustaining the production of autoreactive antibodies (in particular those directed against dsDNA) [92,95,96].…”

Comparison and Analysis of Different Methods for Purification of Autoimmune Antibody Reactive with Single Stranded DNA: A Pilot Study

“…Simple modification of this method will also allow for comparison of anti-DNA IgG and anti-DNA IgM hydrolytic activities, since according literature data, both isotypes have shown to be hydrolytic. 6,7,45 Analysis for antibody hydrolytic activity against a herring sperm ssDNA substrate, via UV spectrophotometry and Lab-on-chip data, have shown that lupus patient antibody isolated via magnetic beads has different reaction kinetics than DNA-se1 indicating that hydrolysis is intrinsic property of the antibody molecule.…”

“…However, since antissDNA antibody has been shown in a limited number of experimental and clinical studies to be both hydrolytic and nephritogenic, it is suggested that it may serve as a strong flare predictor. [2][3][4] The important role of anti-ssDNA antibody is supported by studies in mouse models of nephritogenic lupus in which only anti-ssDNA antibodies were found 6,7 as well as by the findings of Swanson et al, 1 & Spatz et al, 8 that some anti-dsDNA human antibodies are not pathogenic at all. The ultimate goal of this study was to determine the optimal conditions for analysis of the types and activity of highly purified human antissDNA (IgG antibody) in order to gain deeper insight into functional characteristics such as binding, DNA hydrolysis, cytotoxicity and the role of these antibodies in SLE pathogenesis.…”

Catalytic antibodies in patients with systemic lupus erythematosus

“…Polyclonal IgG antibodies purified from the sera of several patients with SLE and patients with hepatitis B showed the RNA-hydrolyzing activities that differed from the weak RNase A-type activities of IgG from the healthy donors (40). Not surprisingly, based on the fact that abzymes are slow catalysts as compared to the kinetic values determined for conventional DNases, the reaction turnover values for DNA-abzymes were two times lower (40 to DNA and were mainly responsible for DNase activity (41,42).…”