Nucleotide-hydrolyzing antibodies from the sera of autoimmune-prone MRL-lpr/lpr mice

Abstract

Abzymes (Abzs) with different enzymic activities have been detected in the sera of patients with various autoimmune (AI) diseases and in AI mice. In this work, electrophoretically homogeneous IgGs were isolated from the sera of MRL-lpr/lpr mice spontaneously developing lupus-like AI pathology. It was shown for the first time that polyclonal IgGs (pIgGs) and their isolated heavy and light chains hydrolyze different nucleoside-5'-triphosphate (NTPs), nucleoside-5'-diphosphate (NDPs), adenosine monophosphate and deoxiadenosine-5'-monophosphate (dAMP), whereas antibodies from the sera of control healthy mice were catalytically inactive. Monoclonal mouse IgGs also effectively hydrolyze nucleotides. The data demonstrate that nucleotide-hydrolyzing activity is an intrinsic property of isolated mouse pIgG and monoclonal IgG. It was shown that various markers of AI pathologies (proteinuria and antibody titers to native and denatured DNA) demonstrating spontaneous development of AI reactions increased in animals with aging and correlated with an increase in Abz relative activity in hydrolysis of nucleotides. The highest increase in AI reaction markers and in Abz enzymic activity was found in mice immunized with a DNA-protein complex.

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

“…The average anti-DNA Abs concentration in the case of (CBAxC57BL)F1 and BALB/c nonautoimmune control mice was estimated to be approximately 0.03-0.04 A 450 units and was comparable with that for healthy autoimmune-prone MRL-lpr/lpr mice (0.032 A 450 units) [29][30][31]. After spontaneous development of SLE in MRL-lpr/lpr mice (depending of individual mice during 4-7 months), it increases to 0.2 A 450 units, but there were no remarkable change in the anti-DNA Abs titers in the case of control nonautoimmune mice during 7-8 months of the experiment [29][30][31].…”

“…After spontaneous development of SLE in MRL-lpr/lpr mice (depending of individual mice during 4-7 months), it increases to 0.2 A 450 units, but there were no remarkable change in the anti-DNA Abs titers in the case of control nonautoimmune mice during 7-8 months of the experiment [29][30][31]. After MRL-lpr/lpr mice immunization with complex of methylated-BSA with DNA (further marked as DNA), the average concentration of anti-DNA Abs increased to approximately 0.6 A 450 units [29][30][31]. It should be mentioned that IgG antibodies from the sera of control 2-7 month-old nonautoimmune CBA and BALB mice and conditionally healthy 2-3 months old MRL-lpr/lpr mice were shown to be catalytically inactive [29][30][31].…”

“…Mice demonstrating all visual symptoms and biochemical indexes of SLE were designated as diseased animals. We have compared healthy (2-3 months of age) and spontaneously diseased MRLlpr/lpr mice with all visible symptoms no older than 7 months [29][30][31]. For a more precise characterization of the various states of these mice, we have evaluated a variety of medical, biochemical, and immunological characteristics of their status including the relative levels of Abs to various autoantigens of abzymes demonstrating different catalytic activities.…”

“…However, specific positive roles have been also proposed for several abzymes. Increase in Abzs activities is associated with a specific reorganization of the immune system including change in differentiation profile and level of proliferation of hematopoietic stem cells of bone marrow as well as lymphocyte proliferation in different organs of SLE and experimental autoimmune encephalomyelitis (EAE) in mice [29][30][31][32]. Different mechanisms of abzymes production were revealed in healthy animals after external immunization and in autoimmune mice during their spontaneous or antigen-induced development of autoimmune processes [29][30][31][32].…”

“…It was shown that abzymes with different activities may be obtained with a significantly higher incidence in autoimmune mouse strains comparing to conventionally used control nonautoimmune mice [51,52]. Immunization of autoimmune-prone MRL-lpr/lpr mice with DNA-protein complexes also results in significantly higher production of anti-DNA Abs and abzymes with DNase activity comparing with nonautoimmune CBA and BALB/c healthy mice [29][30][31]. At the same time, artificial antiidiotypic abzymes can be induced by immunization of animals with different enzymes [23][24][25][26][27][28].…”