0000000000535877
AUTHOR
Varda Rotter
Monoclonal antibody to a DNA-binding domain of p53 mimics charge structure of DNA: anti-idiotypes to the anti-p53 antibody are anti-DNA
Antibodies to DNA are important markers of various autoimmune diseases and can be pathogenic; however, their generation is not understood. We previously reported that anti-DNA antibodies could be induced in mice by idiotypic immunization to PAb-421, an antibody to a DNA-binding domain of p53. We now report that two monoclonal antibodies of moderate affinity (K(D) asymptotically equal to 10(-7)), raised from PAb-421-immunized mice, specifically recognized both PAb-421 and DNA. These antibodies feature multiple arginine residues in the antigen-binding site, a unique characteristic of disease-associated anti-DNA antibodies; nevertheless, these anti-DNA antibodies show specific complementarity …
Autoimmunity to the p53 protein is a feature of systemic lupus erythematosus (SLE) related to anti-DNA antibodies.
The induction of anti-DNA autoantibodies in systemic lupus erythematosus (SLE) patients is problematic because mammalian DNA is poorly immunogenic at best. Here we demonstrate a chain of connected antibodies in SLE patient sera that could account for the induction of anti-DNA antibody, and possibly for some of the pathogenic features of SLE. We now report that SLE patients, in addition to anti-DNA, produce antibodies to the carboxy-terminal domain of the tumour suppressor molecule p53; this p53 domain recognizes damaged DNA. Hence, these anti-p53 antibodies could mimic damaged DNA immunologically. Indeed, SLE sera do contain anti-idiotypic antibodies to a prototypic anti-p53 antibody. Moreo…
Prevalence of Autoantibodies to the p53 Protein in Autoimmune Hepatitis
The target antigens of anti-nuclear autoantibodies in autoimmune hepatitis (AIH) are poorly characterised. Since antibodies to the p53 nuclear protein have been reported in various autoimmune diseases, we have assessed the prevalence of these antibodies in patients with AIH (n = 45), primary biliary cirrhosis (n = 60), hepatitis B (n = 22), hepatitis C (n = 55), and in a control group of subjects with various non-liver diseases (n = 56). A significant proportion of patients with AIH (31%) had elevated levels of autoantibodies to the p53 protein. In contrast, the prevalence of these antibodies in primary biliary cirrhosis (8%) and viral hepatitis (6%) was similar to that in the control group…