Oligonucleotide linked to human gammaglobulin specifically diminishes anti-DNA antibody formation in cultured lymphoid cells from patients with systemic lupus erythematosus.

Abstract

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

SLE: translating lessons from model systems to human disease

“…For example, more than 30 years ago, Borel and colleagues showed that it is possible to prevent lupus in an animal model by inducing tolerance to denatured DNA [31]. About 15 years later, this finding was translated into human disease by showing that a DNA-human IgG conjugate inhibits the formation of antidsDNA antibodies in vitro by lymphoid cells from SLE patients [32]. Such studies eventually led to a clinical trial to evaluate a dsDNA-directed B-cell tolerogen, a synthetic molecule with the ability to bind dsDNA antibodies, thus leading to anergy or apoptosis of B cells, which has shown delayed renal flares and reduction of anti-dsDNA antibodies in a subgroup of patients [33].…”

Immunogenicity of Therapeutic Fusion Proteins: Contributory Factors and Clinical Experience

“…Immunoglobulins, especially IgG subclasses, had long been known to be excellent tolerogenic carriers by virtue of long half-life, favorable pharmacodymamics and their ability to cross-link inhibitory Fc receptors [66]. The fusion protein per se was shown to be tolerogenic [67], a point to which we shall return.…”

Multivalent Compounds for Antigen-Specific B Cell Tolerance and Treatment of Autoimmune Diseases

“…The resulting conjugates were reported to inhibit SLE patient antibodies from binding to calf thymus DNA, and they inhibited the spontaneous formation of antidsDNA in vitro using cultured lymphoid cells from SLE patients [63,64]. Another approach used conjugates of nucleosides and isologous IgG.…”