Ex vivo removal of IgE in atopic asthma by extracorporeal plasmoimmunoadsorption (EPIA): development of a clinical adsorbent.

We have developed an immunoadsorbent (IA) for ex vivo removal of IgE after in vitro screening of matrix (Sepharose and tresyl-activated Toyopearl) and ligand (monospecific rabbit polyclonal anti-IgE antiserum and monoclonal antibodies (Abs) or their Fab fragments). Specific adsorptive capacity (SAC) for IgE was maximal in Sepharose-based IA with both types of Abs. Fab-containing IA on Sepharose retained 70-90% of the SAC of native Ab-containing IA. Toyopearl-based IA showed comparable SAC under static conditions but worked unsatisfactorily under continuous flow conditions. To assess the complement-activating capacity (CAC) of IA in vitro anaphylatoxin (C3a, C4a, C5a) generation was applied. CAC was directly related with the amount of immobilized Ab ligand, without depending on Ab specific activity. Fab-containing IA showed more CAC than native Ab-containing IA, and polyclonal IA more than monoclonal IA. Therefore, IA for IgE apheresis were prepared from native monoclonal Abs and CNBr-activated Sepharose CL 4B under aseptic conditions and packed into a glass column. This IA was used in 17 clinical IgE apheresis treatments of five atopic asthma patients. No substantial side effects were observed; in vivo IA effectively removed IgE from plasma (83 to 98%).

[Clinical immunosorbents on a basis of polymeric matrices]. / Klinicheskie immunosorbenty na osnove polimernykh matrits.

Immobilization of anti-IgE on space-network polymers containing aliphatic amino- and hydrazido groups as a way of producing clinical immunosorbents has been studied. Influence of active group concentration on the specific activity of the immobilized antibodies and sorption dynamics of IgE from plasma of patents are investigated. Immunosorbents can be sterilized by gamma-irradiation without any loss of capacity. It is shown that the immunosorbents can be reused after regeneration. Basing on the results obtained, acrylonitrile- divinylbenzene copolymer with hydrazido groups is considered as the most perspective for production of clinical immunosorbents.

[Immunosorption on active carbon]. / Immunosorbtsiia na aktivnykh ugliakh.

Sorption of specific immunoglobulins in the most obvious mechanism of the detoxicating effect of haemosorption in autoimmune diseases. Biochemical analyses of blood from patients with psoriasis showed that content of immunoglobulins was not distinctly altered before and after haemosorption. Determination of the protein spectrum to find the absorbed components was carried out by means of immunization of rabbits with the carbon suspension, obtained from the patients with psoriasis after haemosorption. Immunoglobulin G constituted the main amount of the absorbed protein. Sorption of albumin was studied in model experiments in order to determine the optimal pore structure of carbon haemosorbents. Capacity of active carbons to the protein sorption depended only on volume of transient pores. These data enabled to work out the recommendations for synthesis of active carbons with improved efficiency to sorption of protein components from blood plasma.

Removal of plasma bilirubin by hemoperfusion in dogs.

The removal of plasma bilirubin by hemoperfusion in dogs with hepatic insufficiency was investigated. The quantity of bilirubin adsorbed from the plasma and from tissue flux during hemoperfusion was measured. The relationships of the mass of removed bilirubin, its initial concentration in the blood and the time of perfusion showed a good correlation. These studies have shown that the anion-exchange resin MCTI-2A used for removal of plasma bilirubin did not alter the electrolyte composition, acid-base balance and the concentration of other measured metabolites.