Immunoadsorption

Immunoadsorption (IAS) is a therapeutic nephrology procedure used to remove toxic and generally pathogenic (disease-causing) substances from the blood using an adsorption system. Adsorption describes the accumulation of substances from gases or liquids on the surface of a solid. The advantage of immunoadsorption compared to other blood purification methods is the possibility to specifically remove the human pathogenic substances from the blood circulation, so that the elimination makes it unnecessary to administer plasma to the affected patient. The result of this procedure is that significantly larger plasma volumes in the extracorporeal (outside the body) circulation can be treated. Furthermore, more drastic reductions in immunoglobulins (antibodies) type G (IgG) and autoantibody levels are possible. Because of this, the procedure plays an important role not only in nephrology, but also in rheumatology, for example. The method has also been used in the therapy of familial hypercholesterolemia (genetically caused excess of cholesterol in the organism).

Indications (areas of application)

Confirmed treatment indications

  • Inhibitory hemophilia – Autoantibodies to factor VIII or factor IX, although rare, are associated with high risk of bleeding and therefore high lethality (mortality relative to the total number of people with the disease). This disease, known as acquired inhibitory hemophilia, occurs with equal frequency in both sexes and is clustered in old age.
  • Dilated cardiomyopathy (DCM) – Pathological enlargement (dilation) of the heart muscle leading to heart failure; the use of immunoadsorption is evidence-based, but this evidence is only secure in autoantibody-positive patients. Dilated cardiomyopathy represents an abnormal enlargement of the myocardium.
  • Kidney transplant recipients – the use of the procedure is particularly indicated in sensitive potential recipients of a donor kidney. The procedure can significantly and relevantly reduce the risk of rejection.
  • Acute humoral graft rejection – immunoadsorption can be used not only preventively, but also in acute rejection.

Possible treatment indications

  • Systemic lupus erythematosus (SLE) – generalized lupus erythematosus is a generalized autoimmune disease, which in its chronic course can affect all organs and leads to massive damage, especially to the skin, joints and kidneys. It is characterized by the appearance of autoantibodies directed against cell nuclear components (antinuclear antibodies, ANA), double-stranded DNA (anti-ds-DNA antibodies) or histones (anti-histone antibodies). The use of immunoadsorption can reduce the occurrence of symptoms, if necessary.
  • Glomerulosclerosis – autoimmune renal diseases such as focal sclerosing glomerulosclerosis or rapidly progressive glomerulonephritis may be able to be slowed in their progression.
  • Guillain-Barré syndrome (GBS; synonyms: Idiopathic polyradiculoneuritis, Landry-Guillain-Barré-Strohl syndrome); two courses: acute inflammatory demyelinating polyneuropathy or chronic inflammatory demyelinating polyneuropathy (disease of the peripheral nervous system); idiopathic polyneuritis (diseases of several nerves) of the spinal nerve roots and peripheral nerves with ascending paralysis and pain; can occur, for example, after a bacterial infection with Campylobacter pylori and contribute to damage of the gangliosides of the central nervous system by endotoxins (lipopolysaccharides). The success of adsorption of autoimmune antibodies has not yet been adequately demonstrated.
  • Rheumatoid arthritis – this disease, triggered by autoantibodies, can lead to severe damage to the organs and skeletal system if not adequately treated. Immunoadsorption could serve as another therapeutic option.
  • Thrombotic thrombocytopenic purpura – in TTP, also known as Maschcowitz syndrome, characterized by fever, hemolytic anemia (anemia caused by the premature breakdown or disintegration of red blood cells), and renal insufficiency (kidney weakness), immunoadsorption can support therapy with von Willebrand protease substitution.

The procedure

Implementation of immunoadsorption

  • At the beginning of the performance of the therapeutic procedure, plasma separation is performed. When separating plasma from the other blood components, care must be taken to maintain adequate plasma quality. This is made possible by centrifugation. Compared to other separation methods, centrifugation is a particularly time-effective method.
  • Through a specific adsorption machine, the present plasma of the patient is passed over special apheresis columns. The apheresis columns represent an important means of detoxification of the blood. A relatively firm binding of the antibodies present in the plasma now takes place on the present columns. The plasma components that were unable to bind to the columns are subsequently associated with the corpuscular blood components (blood cells). Once this step is done, a reinfusion of the plasma now present in the whole blood is performed into the patient.
  • The extracorporeal volume usually does not exceed 200-300 ml and is thus comparable to other detoxification procedures such as plasma exchange. Through a CVC (central venous catheter) or peripheral veins, the necessary blood sampling is performed. A total blood flow of 50-80 ml per minute is achieved. After plasma separation, another 30 ml per minute flows along the apheresis columns. Buffers and a rinsing solution must be added for the adsorption device to function.
  • To maintain the effectiveness of the process, it is necessary that the column quality is optimal. Furthermore, it is critical that extracorporeal coagulation (blood clotting) is prevented, as this can further reduce the effectiveness of immunoadsorption. As a result of this realization, combined anticoagulations with citrate and heparin are nowadays used in immunoadsorption. However, since treatment of patients at risk of bleeding must also be performed, so-called extracorporeal anticoagulation is used for anticoagulation. The special feature of this treatment strategy is the antagonization (activation of the antagonist) of heparin by protamine before reinfusion into the patient’s bloodstream. Protamine can reduce the effect of heparin in a salt formation reaction.

Since the development of immunoadsorption, various systems have become widely used, the majority of which bind immunologically active peptides (small proteins) via two-column systems. In two-column systems, one column is alternately loaded while the second column is regenerated. Adsorption of immunologically active substances

  • Adsorption of immunoglobulins occurs by different mechanisms and methods depending on the system. For example, sheep antibodies to human immunoglobulin can be used, which are then bound on a special matrix. Depending on the system and manufacturer, the specificity for the immunoglobulin subclasses varies.
  • Another option for immunoadsorption is the use of staphylococcal proteins as ligands for the antibodies. This allows specific binding of IgG antibodies.