Amelioration of Experimental Autoimmune Myasthenia Gravis Rats Using 4-Mercaptoethylpyridine-based Adsorbent

摘要

Immunoadsorption is an important type of blood purification therapy normally used in clinic, and has proven effective in treating myasthenia gravis (MG) and a range of other autoimmune diseases. Protein ligands, such as recombinant Protein A, antibody and autoantigens, are usually employed for immunoadsorbents. They have high specificity for target molecules, but also suffer from the drawbacks mainly associated with their protein nature, such as high cost and low stability. Thus, synthetic compounds are being explored for production of specific adsorbents for the treatment of autoimmune diseases. In this work, 4-mercaptoethylpyridine (MEP)-based adsorbent, an adsorbent previously found to have affinity with immunoglobulin (Ren et al., 2009), was investigated for its potential effects in treating MG. Animal model of experimental autoimmune myasthenia gravis using Lewis rats was developed, and treated by whole blood apheresis. Adsorption columns were prepared with a sepharose-based adsorbent coupling MEP as immobilized ligands. The results showed that, the symptoms of treatment group rats were apparently improved after treatment compared to the controls, with clinic score decreasing from 2.08 ± 0.38 to 1.25 ± 0.27. After a treatment using 4 ml adsorbent for a total 24 ml of blood, the amount of white cells of the rats was reduced by 43.7 ± 6.4 %, while the level of red cells were not significant changed. ELISA essays showed that the serum concentrations of IgG, IgM, acetylcholine receptor antibody (AChRab), complement 3 and IL-17 were reduced by 31.5 ± 7.6 %, 24.4 ± 6.1 %, 27.5 ± 7.4 %, 22.3 ± 3.6 % and 21.7 ± 5.8 %, respectively. No abrupt bounce of AChRab concentration was observed in one weeks after the treatments (Figure 1). This study demonstrated that MEP-based adsorbent could not only remove pathogenic autoantibodies directly from blood as Protein A adsorbents could, but also further regulate the immune system by eliminating other inflammation related molecules and cells.