A new device for specific extracorporeal immunoadsorption of anti-DNA antibodies. In vitro and in vivo results.
Selective removal of anti-DNA antibodies could be an alternative to therapeutic plasma exchange in patients with active systemic lupus erythematosus. The method is based on the immobilization by covalent binding of double-stranded, calibrated, 0.3-kb DNA fragments on a microporous, methylated, polyacrylonitrile membrane. This enables linkage of 60 micrograms of DNA per cm2 of apparent surface area. In vitro, perfusion of 100 ml of plasma maintained at 37 degrees C through 650 cm2 of dsDNA linked to the membrane, at a flow rate of 1.5 ml/min for 60 min, resulted in the removal of 49-89% of anti-DNA IgG without any changes in plasma protein or IgG levels. During a therapeutic plasma exchange, perfusion of the plasma through 1.5 m2 of membrane, at a flow rate of 25 ml/min, initially removed 92% of the anti-dsDNA antibodies entering the adsorbent and 25% at 120 min, indicating a progressive saturation of the binding capacity. Clinical immunoadsorption, at a plasma flow rate of 20-40 ml/min through 2 m2 of membrane, removed more than 50% of anti-dsDNA IgG within 60 min. Microporous membranes are able to irreversibly bind large amounts of antigenic ligands, and enable the selective removal of pathogenetic immunoglobulins or circulating factors.