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

• Published in: Biologicals 2005-06, Vol.33 (2), p.111-116
• Main Authors: Thorpe, Susan J., Fox, Bernard J., Dolman, Carl D., Thorpe, Robin
• Format: Article
• Language: English
• Subjects: ABO Blood-Group System - immunology; Drug Industry; Hemagglutination Tests - methods; Humans; Immunoglobulins, Intravenous - immunology; Reference Standards
• ISSN: 1045-1056; 1095-8320
• DOI: 10.1016/j.biologicals.2005.02.002

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.