title: Anti-A and anti-B activity in batches of different intravenous immunoglobulin products determined using a direct haemagglutination method.
abstract: 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.
authors.affiliation: Division of Haematology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, UK. sthorpe@nibsc.ac.uk
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Thorpe
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Fox
authors.forename: Carl D
authors.initials: CD
authors.lastname: Dolman
authors.forename: Robin
authors.initials: R
authors.lastname: Thorpe
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D004345:Drug Industry; D006386:Hemagglutination Tests / Q000379:methods*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D012015:Reference Standards
chemical_list: D000017:ABO Blood-Group System; D016756:Immunoglobulins, Intravenous