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

摘要

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.