DNA-hydrolyzing autoantibodies

Abstract

Catalysis by antibodies could be a frequent phenomenon if the immune system generates a sufficiently diverse number of antibody-active sites, some of which may possess catalytic activity. A catalytic antibody can be expected to do more damage than one that simply binds antigen. The best biochemical marker of systemic lupus erythematosus (SLE) is presence of autoantibodies to DNA. In the present article, we describe the DNA-hydrolyzing activity of DNA-binding autoantibodies purified from SLE patients. The substrates employed were supercoiled plasmid, radiolabeled plasmid fragments, and oligonucleotides. Hydrolysis of DNA by the antibodies was indicated by the appearance of fragments visualized by ethidium bromide staining of agarose gels or autoradiography of polyacrylamide gels. Changes in linear dichroism values were also indicative of DNA hydrolysis. The antibody activity was purified by protein A-sepharose chromatography, high-performance liquid chromatography gel filtration, and DNA-affinity chromatography. Scrupulous control studies were done to demonstrate that DNA-hydrolyzing activity really belongs to the antibodies. Purified Fab fragments showed hydrolyzing activity, whereas the Fc fragment was inactive. The specificity of DNA cleavage was investigated, and the rate parameters of hydrolysis by antibodies and conventional nucleases were compared.

Natural Catalytic Antibodies – Abzymes

“…Concentrations of DNA and anti-DNA Abs are especially high in patients with systemic lupus erythematosus (36% of SLE patients) [61,89,90]. Increased concentrations of DNA and anti-DNA Abs were also found in the blood of patients with other different ADs: polymyositis (49%), MS (17%), primary Sjogren's syndrome (18%), AI thyroid diseases (23%), myasthenia gravis (6%), and rheumatoid arthritis (7%).…”

“…It is suggested that DNA-hydrolyzing Abs generated in patients with SLE have anti-idiotypic nature [36,90]. The authors suggest that these DNA-hydrolyzing Abs are anti-idiotypic Abs to topoisomerase I, because in the blood serum of patients with SLE an increased level of Abs against this enzyme was noted.…”

“…Increased concentrations of DNA and anti-DNA Abs were also found in the blood of patients with other different ADs: polymyositis (49%), MS (17%), primary Sjogren's syndrome (18%), AI thyroid diseases (23%), myasthenia gravis (6%), and rheumatoid arthritis (7%). AI hepatitis, [61,89,90], and also with lympho-proliferative [61] and some viral diseases (e.g., viral hepatitis and AIDS) [62]. Although some viral diseases like AIDS and viral hepatitis are not related to ADs, they significantly influence the immune status of patients.…”

Recognition and Degradation of Myelin Basic Protein Peptides by Serum Autoantibodies: Novel Biomarker for Multiple Sclerosis

“…We showed that sera from normal controls do not exhibit MSdefined cleavage activity. The rigorous purification scheme first developed for the isolation of "natural abzymes" (47) ensures that the activity measured is abzyme-mediated and cannot be ascribed to contaminating enzymes. Among the OND patients who were studied we could find only 9% positives cases of abzyme catalysis.…”

Catalytic antibodies in patients with systemic lupus erythematosus

“…Therefore, emergence and enhanced titers of hydrolytic antibodies might represent a universal phenomenon of inflammatory response. During early 1990s, Gabibov and colleagues reported that autoantibodies purified from the sera of patients with SLE and other autoimmune diseases cleave phosphodiester bonds (2,38,39). 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).…”