Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease, characterized by polyclonal B-cell proliferation and a variety of autoantibodies. Common symptoms include painful and swollen joints, fever, swollen lymph nodes, and red rashes on the face. In addition, proliferative lupus nephritis is one of the most severe aspects of SLE, potentially leading to irreversible kidney failure. Furthermore, as the increase of anti-dsDNA antibody levels in SLE appears to be associated with an increased risk of flare and renal involvement, reducing anti-dsDNA antibodies may be a goal of therapy in this disease.
Abetimus (also known as LJP 394) is an immunosuppressant consisting of four double-stranded DNA (dsDNA) oligonucleotides.
Abetimus is capable of crosslinking anti-dsDNA antibodies on the surface of B cells and decreases anti-dsDNA antibodies levels. Thus, Abetimus has the potential for research on systemic lupus erythematosus. Particularly, Abetimus reduces circulating anti-dsDNA antibodies through at least two mechanisms. First, Abetimus possibly acts through the formation of small soluble complexes that do not appear to result in significant activation of the complement system. Second, Abetimus binds B cells without activating T cells, causing them to undergo apoptosis and reducing anti-dsDNA antibody production. Indeed, Abetimus appears to induce B-cell tolerance by cross-linking anti-dsDNA surface immunoglobulin receptors on B cells and triggering signaling pathways leading to B-cell anergy or apoptosis.
Abetimus shows excellent efficacy in vivo experiments. In the systemic lupus model mice, Abetimus (3-300 μg/mouse, i.v. twice weekly) significantly lowers titers of anti-dsDNA, lowers numbers of anti-dsDNA-secreting spleen cells, and less adverse renal histopathology than control mice. Moreover, Abetimus has a pharmacokinetic half-life ranging from 40 min to 1 h in mice.
In summary, Abetimus is an immunosuppressant consisting of four dsDNA oligonucleotides. It has the potential for research on systemic lupus erythematosus.