ANALYSIS OF ANTI-DNA ANTIBODIES IN SLE BY A MONOCLONAL ANTI-IDIOTYPE (AUTOIMMUNITY, NETWORK)

Abstract

The spontaneous production of antibodies to DNA is characteristic of murine and human systemic lupus erythematosus (SLE). These antibodies appear to correlate with clinical activity of SLE and they have been implicated in tissue damage.;To probe the heterogeneity and the regulation of production of anti-DNA antibodies in SLE we have generated a monoclonal anti-idiotypic antibody, 3I, which recognizes a cross-reactive idiotype on the kappa light chains of human anti-DNA antibodies.;Analysis of sera from normal individuals, SLE patients, and healthy relatives has revealed different patterns of 3I expression of the idiotype recognized by 3I. Normals have a low titer of 3I idiotype by radioimmunoassay (RIA) and show absence of cationic 3I reactive antibody bands on isoelectric focusing (IEF) gels. DNA binding assays reveal no antibodies. In serum from approximately 90% of SLE patients, when anti-DNA antibodies are detectable in conventional DNA binding assays, 3I reactivity by RIA is elevated above that seen in normal individuals and cationic 3I reactive bands are present on IEF gels. Other sera from SLE patients with no anti-DNA activity in conventional assays have high titered 3I reactivity and cationic 3I reactive antibody bands. These sera can be shown to have 3I reactive anti-DNA antibodies when they are analyzed under dissociating conditions.;Many healthy relatives of SLE patients have been analyzed and have elevated expression of the 3I idiotype, yet no cationic bands and no DNA binding antibodies.;From these studies, we conclude that regulation of idiotype expression can be separated from antigenic specificity and that idiotype-positive DNA binding antibodies are more cationic than idiotype-positive antibodies that have no specificity for DNA.