title: Donor screening reduces the isoagglutinin titer in immunoglobulin products.
abstract: BACKGROUND
  Hemolysis reaction is a rare class effect of therapy with intravenously administered human normal immunoglobulin (IVIG). Anti-A/B isoagglutinins (isohemagglutinins) originating from donor plasma are considered a probable risk factor for hemolysis. We hypothesized that screening and exclusion of plasma obtained from donors with high isoagglutinin titers from the manufacturing process would produce a meaningful reduction of anti-A/B isoagglutinin titers of the final IVIG product.
  
  
  METHODS
  A donor screening method for anti-A isoagglutinins using an automated indirect agglutination test (IAT) in gel cards was developed. Industry-scale donor plasma pools and final IVIG product were prepared according to the manufacturing process of Privigen (human 10% liquid IVIG). Anti-A/B isoagglutinin levels were measured by IAT, direct agglutination test, and a flow cytometry-based assay.
  
  
  RESULTS
  Screening of plasma from 705 randomly selected donors identified 6.8% donors with high anti-A isoagglutinin titers in plasma. Exclusion of plasma from these donors resulted in a one-titer-step reduction of anti-A isoagglutinin in laboratory-scale pooled plasma. The same donor screening method applied to industry-scale production resulted in exclusion of 5.1% of donors and produced a one-titer-step reduction of both anti-A and anti-B isoagglutinin titers in the final IVIG product.
  
  
  CONCLUSIONS
  Anti-A/B isoagglutinin titers in IVIG products can be reduced on an industrial scale through implementation of anti-A donor screening, which may lower the risk of hemolysis after IVIG therapy.
authors.affiliation: Biochemical Quality Control, Berne, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Siani
authors.affiliation: Biochemical Quality Control, Berne, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Willimann
authors.affiliation: Product Development, CSL Behring AG, Berne, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Wymann
authors.affiliation: Biochemical Quality Control, Berne, Switzerland.
authors.forename: Adriano
authors.initials: A
authors.lastname: Marques Antunes
authors.affiliation: Biochemical Quality Control, Berne, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Widmer
mesh_terms: D000017:ABO Blood-Group System / Q000097:blood / Q000737:chemistry; D001782:Blood Donors; D046148:Donor Selection / Q000379:methods*; D005260:Female; D006388:Hemagglutinins / Q000097:blood / Q000737:chemistry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000737:chemistry*; D008297:Male; D010949:Plasma / Q000737:chemistry*
chemical_list: D000017:ABO Blood-Group System; D006388:Hemagglutinins; D016756:Immunoglobulins, Intravenous