Selective Removal of Circulating Immune Complexes from Patient Plasma

Abstract

The principle of a patient-specific immunoadsorber (PsIA) is demonstrated. Studies with model systems (HSA/anti-HSA) on immobilization, stability, and leakage form the basis for the presented fast-performance liquid chromatography (FPLC) and batch experiments, which were conducted using two different protein A adsorbers and autologous and heterologous PsIA systems. Experiments to determine the binding capacity of protein A adsorbers and PsIAs are described. In all experiments, the adsorption of plasma IgG, total protein, and C1q and C3d circulating immune complexes were measured. Plasma of patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) was investigated. Analysis was performed in both the initial plasma and the flow-through or supernatant. Results of the investigations using FPLC and batch experiments were compared. Autologous PsIA systems are suitable for the selective removal of elevated levels of circulating immune complexes in the plasma.

MS characterization of apheresis samples from rheumatoid arthritis patients for the improvement of immunoadsorption therapy – a pilot study

“…As immune complexes – that presumably were present on the Prosorba ® columns – were dissociated under acidic conditions 39 which were used to eluting the retained proteins from the columns, we cannot determine whether the proteins that were visualized on the 2‐D gels originally were part of such complexes or not. The somewhat different protein compositions that were observed in our studies when different elution conditions (citric acid, pH 5, and acetic acid, pH 3, respectively) were applied may in fact point toward the presence of immune complexes on the columns.…”

The low-throughput protein A adsorber: an immune modulatory device. Hypothesis for the mechanism of action in the treatment of rheumatoid arthritis

“…If the scavenging capacity is insufficient or overloaded, deposition of IC can lead to inflammation. 34 There is evidence that autoAb or IC are involved in various kinds of autoimmune diseases. Removing the pathogenic IC from patient's plasma is supposed to be an efficient way for the treatment of IC-based chronic inflammatory diseases such as RA and systemic lupus erythematosus (SLE).…”

“…Removing the pathogenic IC from patient's plasma is supposed to be an efficient way for the treatment of IC-based chronic inflammatory diseases such as RA and systemic lupus erythematosus (SLE). 34 In contrast to conventional apheresis, selective adsorption of IC or specific adsorption of pathogenic autoAb without depleting other plasma proteins including regular Ig would be advantageous. Immune adsorption employs physical (e.g., electrostatic) or chemical avidity to capture pathogenic molecules.…”