Natural catalytic antibodies in norm, autoimmune and viral diseases

摘要

In patients with autoimmune diseases (ADs) autoantibodies (Abs) directed to polysaccharides, nucleic acids, proteins, peptides, nucleoprotein complexes, and enzymes with different catalytic functions may be induced spontaneously by primary antigens and can have characteristics of the primary antigen, including the catalytic activity of idiotypic and/or antiidiotypic Abs. The discovery of IgG specifically hydrolyzing intestinal vasoactive peptide in the sera of asthma patients (Paul S., 1989) stimulated of the studies of natural catalytic Abs (abzymes; Abzs). Detection of Abzs was shown to be the earliest indicator of development of different ADs. At the early stages of ADs, the repertoire of Abzs is usually relatively small but it greatly increases with the progress of the disease, leading to the generation of catalytically diverse abzymes with different activities and functions. Some Abzs are cytotoxic and can play an important negative role in the pathogenesis of AI pathologies, while positive roles have been proposed for other abzymes. During the spontaneous development of profound SLE-like pathology in mice, a specific reorganization of the immune system leads to conditions associated with production of Abzs with low catalytic activities (conditionally pre-diseased mice). A significant increase in the relative Abz activities associated with a transition from pre-diseased to diseased mice is correlated with additional changes in the differentiation and proliferation of bone marrow hematopoietic stem cells and lymphocyte proliferation in different organs. Different mechanisms of Abzs production are observed for healthy mice immunized externally and for autoimmune mice during the spontaneous development of pathology. New data concerning Abzs with different catalytic activities in various ADs, possible reasons of their catalytic heterogeneity, possible roles of abzymes and their exceptional multiplicity in the pathogenesis of different ADs, and possible uses of the abzyme activity for diagnostic of AI diseases are discussed.