Idiotypes of anti-DNA antibodies

Abstract

This chapter discusses the characteristics of anti-DNA idiotypes, the clinical expression of such idiotypes, their possible pathogenic role in autoimmune diseases, and the therapeutic potential of treating autoimmune diseases by manipulation of such idiotypes. Over 30 idiotypes of anti-DNA antibodies have been described, majority of which were described on human hybridoma derived monoclonal antibodies from the peripheral blood lymphocytes of lupus or leprosy patients. However, some were identified on monoclonal anti-DNA antibodies derived from normal individuals. Most of the common DNA antibody idiotypes are of IgM isotype, the majority of which bind to synthetic polynucleotides in addition to DNA. One of the most investigated anti-DNA idiotypes is the 16/6 Id, which was initially identified as anti-single-stranded (SS) DNA antibody. Subsequent analysis demonstrated its ability to bind to other polynucleotides, including nucleic acids, nucleoproteins, cell membranes, and phospholipids. SA1, another related anti-DNA antibody, is a 16/6+ hybridoma monoclonal antibody derived from the fusion of lymphocytes from a patient with polymyositis. It shows much stronger binding to native DNA than the original 16/6 antibody, and the idiotype is located on the heavy chain variable region. An additional human anti-DNA monoclonal antibody (MIV-7) was reported by the group of Shoenfeld et al., which was generated by an in vitro immunization technique in which normal lymphocytes were stimulated by an anti-idiotypic antibody to an antimouse mammary tumor virus.