A DNA-nicking activity was detected in the sera of patients with various autoimmune pathologies and was shown to be a property of autoantibodies. The DNA hydrolyzing activity, which was purified by affinity and high-performance liquid chromatography, corresponded in size to immunoglobulin M (IgM) and IgG and had a positive response to antibodies to human IgG. The DNA hydrolyzing autoantibodies were stable to acid shock and yielded a DNA degradation pattern that was different from that of deoxyribonuclease (DNase) I and blood DNase.

Blood sera of patients with autoimmune diseases soleroderma @cl), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) have been shown to yield a specific immune response to topoisomerase I, the product of expression of a cDNA fragment cloned into lZgtl1 and monoclonal antibodies (MAB) to the enzyme. The 'topoisomerase test' is no1 absolutely specific for Scl. The stable positive response of autoimmune sera to anti-topoisomerase monoclonal antibodies bus a specific character and is associated with the interaction of the Fab fragment of MAB krith the IgG fraction of autoimmune serum. The response observed indicates the induction of anti-idiotypic antibodies against topoisomerase. The anti-idiotype, isolated by HPLC and affinity chromatography demonstrated the following functional activities: (i) the lnnnunologicol reaction against DNA; (ii) high-affinity DNA-binding with topoisomernse-s@lk consensus; (iii) ability to compete with the native enzyme for biding with DNA and MAB to topoisomerase; (iv) immunological reaction against MAB to topoisomerase. Autoimmunity; Topoisomcrase I; Antiidiotypic antibody; Fusion protein; MPLC of autoimmune sera Production of specific antibodies against various physiologically active compounds, their precursors, transient state analogs and biopolymers has recently gained a new stimulating aspect and entered another phase due to the development of a special field of immunochemistry and enzymology, viz. the catalysis by antibodies or 'abzymcs' [l,Z] which has wide prospects for use both in fundamental research and for practical purposes.Marked progress in the new field of abzymes has been so far achieved regarding only a limited number of biologically significant chemical transformations and mostly concerns chemistry of proteolysis 131. To our knowledge, for example, one of the most interesting objects, DNA, has not been considered yet as an antibody substrate. Many difficulties in this field are connected with the problem ofchoosing an adequate model for DNA chemical transformations and a design of the corresponding transient states.

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