The long-term objective of this proposal is to develop an extracorporeal sorbent based treatment for systemic lupus erythematosus (SLE) and other immunologic disorders. A defining feature of SLE is the presence in the blood of anti-DNA antibodies (Ab), the level of which is correlated with the severity of disease symptoms. Current treatments are marginally effective or limited by severe side effects. The BioLogic-DT sorbent-based hemodialysis system has proven useful in the treatment of liver failure with coma. This technology has been enhanced by combining it with a PF auxiliary system which permits the direct treatment of plasma with powdered sorbents to remove large or protein bound molecules. Use of DNA immunosorbent in the PF unit of the BioLogic-DTPF will provide a therapy for the hematologic manifestations of acute exacerbations of SLE while reducing the anti-DNA Ab level. DNA will be bound to activated charcoal which has been primed with trichlorovinylsilane using gamma radiation, and quantified using standard methods. The capacity of DNA-charcoal to bind monoclonal anti-DNA Ab from purified protein solution or serum will be determined using an ELISA method. The rheologic properties of the DNA- charcoal suspension affecting its behavior in the PF sorbent pumping system will also be evaluated.
Systemic lupus erythematosus (SLE) is a chronic, relapsing immune disorder, the severity of which is linked to anti-DNA antibody levels. The Lupus Foundation estimates that approximately 1.4 million Americans have SLE, and that 75% of patients will experience severe episodes which may be treatable with DNA immunoadsorption. DNA immunoadsorption has the potential to reduce morbidity and organ damage in these patients by reducing or eliminating the anti-DNA antibodies and possibly obviating the need for drug therapies with severe toxic side effects.
