New trends in specific immunoadsorption

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Abstract

Plasma exchange is widely accepted to remove pathogenic substances from patients' blood that cannot be eliminated otherwise like cholesterol in severe forms of familial hypercholesterolaemia or immunoglobulins and circulating immune complexes (CIC) in many autoimmune disorders. But dilution of other plasma proteins, as well as side effects and costs of substitution fluids, limit its efficiency. In immunoadsorption, the pathogen is bound specifically, generally no substitution fluids are needed and plasma can be conducted over the immunoadsorption columns as often as needed to achieve any reduction that one aims at, in some instances below the detection limit (e.g. HLA-antibodies in transplantations). The frequency of aphaereses is determined by the speed of the patients' improvement and the rebound of the eliminated substance, which can in some disorders be slowed down or stopped by concomitant immunosuppression. Generally, immunoadsorption is used in patients, where less expensive and demanding treatment options have failed, like severe hypercholesterolaemia, autoimmune disorders or hyperviscosity syndromes.

Introduction

Plasma exchange treatment (PE) is used to remove a pathogenic or pathologically elevated substance from the patient's blood and substitute plasma by normal exchange fluids, mostly either human albumin or fresh frozen plasma. It is very successful in a large number of disorders with known or supposed pathogens like Guillain–Barré syndrome (GBS), Myasthenia gravis and other autoimmune disorders and in hyperlipoproteinaemia. Thrombotic thrombocytopenic purpura is the only disorder, where not only the pathogen withdrawal, but also the repletion of a normal plasma constituent, the von Willebrand factor cleaving protease has been proven to be an important element of PE. In all other disorders it is assumed that reduction of one single pathogen like elevated cholesterol in familial hypercholesterolaemia or the combination of immunoglobulins with factors of the complement cascade are the acting principle of PE. So it was reasonable to develop immunoadsorption (IA) to eliminate the specific pathogen from the patient's blood by apheresis and to save replacement solutions. In IA, no dilution of normal plasma proteins occurs, so larger plasma volumes can be treated, leading to a steep decrease of the pathogen, in some disorders even below the detection limit. We describe the rationale and indications for specific immunoadsorptions (Table 1).

Section snippets

LDL

Hypercholesterolaemia is one of the leading causes of morbidity and mortality from vascular causes. Even patients with normal cholesterol levels profit from lipid lowering [1]. In high-risk patients with coronary heart disease, vascular occlusive disease or diabetes, where cholesterol cannot be reduced below 200 mg/dl by drugs, lipids should be lowered by apheresis. In 1981 Stoffel et al. introduced LDL apheresis into clinical medicine [2], thus improving Thompson's method of lipid lowering by

Neurological disorders

Plasma exchange has been successfully used in many disorders to remove circulating autoantibodies thus causing remission of the disease, e.g. in acute Guillain–Barré syndrome (GBS) and decompensated myasthenia gravis and Eaton–Lambert-syndrome.

But pathogenic auto- and alloantibodies are often produced abundantly with high tissue concentrations, so that plasma exchange of 100–150% of patient's plasma volume can only take off a very small percentage of pathogenic IgG. In immunoadsorption up to

Immunoadsorption as haemorheotherapy

Rheological therapy aims at an improvement of organ perfusion by removing large plasma proteins that account to a high degree for increased plasma viscosity [40]. Borberg and coworkers [41], [42] describe their concept of rheohaemapheresis by cascade filtration or immune adsorption.

Acknowledgments

We thank Dieter Wiebecke for critical reading of the manuscript.

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