In vitro studies were undertaken to determine whether the level of anti-DNA antibody can be modulated in humans with systemic lupus erythematosus (SLE). DNA fragments of different sizes, i.e., oligonucleotide (N20-30) or oligonucleotide (N10-100), were covalently linked either to human gammaglobulin (HGG) and used as tolerogens or to keyhole limpet hemocyanin and used as immunogens. Experiments were done to determine whether such tolerogens specifically diminish antibodies to denatured DNA, native DNA, or both. PBL were obtained from 87 patients with SLE, 55 of whom spontaneously produced anti-DNA antibodies in vitro. Furthermore, of these 55 test subjects 23 made anti-DNA antibodies in response to antigen challenge in vitro. Exposure of PBL to tolerogenic oligonucleotide-HGG reduced spontaneous antibody formation in 34 of the 55 patients' PBL and abrogated the in vitro-induced response in all instances. The suppression was tolerogen specific. In some SLE patients lymphoid cells were suppressed by both (N10-100)-HGG and (N20-30)-HGG, while in others lymphoid cells were suppressed by only one. Longitudinal studies of spontaneous antibody production showed that the same tolerogens consistently reduced anti-DNA antibody formation in lymphoid cells of 12 patients on several occasions over a 2-yr interval, but in 8 others the results were either variable or inconsistent. In contrast, tolerogens consistently abrogated the antigen-induced response in all 23 patients' PBL. These results obtained in humans in vitro suggest that the principle of carrier-determined tolerance could be applied as a specific therapy for SLE in vivo.
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