Ig‐Therasorb Immunoadsorption for Selective Removal of Human Immunoglobulins in Diseases Associated with Pathogenic Antibodies of All Classes and IgG Subclasses, Immune Complexes, and Fragments of Immunoglobulins

Abstract

Therasorb immunoadsorption (IA), by selectively eliminating pathogenic substances from the circulation, allows for successful therapy of previously insufficiently treatable diseases. Molecules (specific polyclonal sheep antibodies) coupled to a matrix (Sepharose CL 4B) selectively bind plasma components in extracorporeal circulation. This procedure has been established in the treatment of various diseases. Examples are familial hypercholesterolemia (LDL-Therasorb) and selected autoimmune diseases (Ig-Therasorb). Ig-Therasorb IA has been performed in a variety of clinical indications, primarily in the treatment of autoimmune diseases. In most cases, Ig-Therasorb IA has been applied in patients who have failed to respond to conventional therapy with a high rate of clinical improvement. In defined groups of patients with autoimmune diseases and alloantibodies, immunoadsorption can now be considered an established therapeutic means. The fast and efficient removal of immunoglobulins obviously exceeds the efficiency of conventional plasma exchange by far. Autoimmune diseases could be induced by balanced and nonbalanced immunity. The importance of autoantibodies remains unclear, but the efficacy of Ig-Therasorb IA suggests a key role for them. In addition to the established indications for removal of immunoglobulins, there may be a number of promising new indications.

Immunoadsorption Therapy (Therasorb) in Patients with Severe Lupus Erythematosus

“…While a number of case reports about the successful use of plasmapheresis in acute SLE exist in the literature (6, 10, 19, 22), no benefit could be found when plasmapheresis was compared to cytotoxic treatment alone in controlled studies of lupus nephritis (18, 29). The technical disadvantages of removing whole plasma, namely the need for the substitution of plasma constituents and the lack of specificity in the components removed, are overcome by using immunoglobulin‐specific adsorption devices including anti‐human IgG, hydrophobic amino acids, protein‐A and C1q (3, 11, 13, 15). Individual cases and small series of IAS applications in SLE have been published (11, 14, 20, 21, 22, 23, 24, 25, 26).…”

A high‐affinity monoclonal anti‐IgE antibody for depletion of IgE and IgE‐bearing cells

“…In accordance with the Biacore data, we found that sepharose‐bound mAb12 is functional and 5 mg mAb12 allowed a more than 90% depletion of IgE from 20 ml serum containing IgE levels of more than 10 000 IU/ml after only one cycle. It should thus be possible to deplete IgE from 4000 ml plasma with 1 g of adsorbed mAb12 per patient and per cycle which is much less than what is used in existing products (35, 36). The amount of mAb12 needed for IgE depletion may be even scaled down because of the high affinity of mAb12.…”

“…Technologies for extracorporeal immunoadsorption are nowadays highly developed, bear a low risk of side‐effects and are frequently applied in case of antibody‐mediated autoimmune disorders for the removal of IgG antibodies which are present at 100 000 fold higher concentrations than IgE (35, 36).…”

RheoSorb: A Specific Adsorber for Fibrinogen Elimination in Clinical Situations with Impaired Rheology

“…In the TheraSorb system, originally developed for low‐density lipoprotein LDL apheresis, the principle of affinity chromatography is applied for selective removal of substances from plasma. As an example, in the Ig‐TheraSorb system, used for elimination of immunoglobulins (7), specific antibodies, recognizing human immunoglobulins, are covalently coupled to the solid matrix (Sepharose CL‐4B, Amersham Biosciences, Uppsala, Sweden). The mobile phase (the human plasma) passes the solid matrix, and the human immunoglobulins bind to the stationary antibodies, thereby depleting the plasma of the target substance (Fig.…”