Anti-A and anti-B activity in batches of different intravenous immunoglobulin products determined using a direct haemagglutination method.

The European Pharmacopoeia requires that manufacturers assess intravenous immunoglobulin (IVIG) products for antibodies against blood groups A and B using an indirect anti-globulin test (AGT). However, this method suffers from the disadvantage that the anti-globulin reagent may be neutralised by excess IgG and invalidate the data generated. In view of this, we have used a direct microtitre-based haemagglutination method to screen batches of IVIG products from five manufacturers for anti-A and anti-B, and compared the titres with those reported by the manufacturers. The range of reported titres varied 32-fold across the different products, whereas virtually all the direct method titres fell within a 4-fold range for each specificity. This indicated that the discrepancies in reported titres were due to inconsistencies in manufacturers' testing methodology and/or interpretation of results. Our finding that the anti-globulin reagent used to bring about agglutination of anti-A- or anti-B-sensitised erythrocytes in the AGT was neutralised by excess IgG at least down to a 1 in 8 dilution of IVIG (from 5% (w/v) IgG) casts serious doubts on the suitability of the AGT for testing high immunoglobulin concentration products.     

Immunotoxins containing ricin or its A chain

In this chapter we describe the development of first generation immunotoxins containing ricin and its A chain. The roles of the ligand, linker and toxin in generating highly specific in vivo reagents are discussed. The problems associated with first generation immunotoxins in the clinic, and the subsequent development and performance of second generation reagents are described. Finally, future directions for the successful application of these reagents to the therapy of cancer, autoimmunity, transplantation, and infectious diseases are outlined.     

Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

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