title: Anti-red blood cell antibodies, free light chains, and antiphospholipid antibodies in intravenous immunoglobulin preparations.
abstract: BACKGROUND
  Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunoglobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).
  
  
  OBJECTIVE
  To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.
  
  
  METHODS
  Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCI and 0.01 M phosphate-buffered saline, pH 7.4, with or without a further twofold dilution in a low ionic strength solution.
  
  
  RESULTS
  A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.
  
  
  CONCLUSIONS
  Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism.
authors.affiliation: Center for Laboratory Medicine Dr. Risch, Liebefeld-Bern, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sakem
authors.forename: Katja
authors.initials: K
authors.lastname: Matozan
authors.forename: Urs E
authors.initials: UE
authors.lastname: Nydegger
authors.forename: Guenter
authors.initials: G
authors.lastname: Weigel
authors.forename: Andrea
authors.initials: A
authors.lastname: Griesmacher
authors.forename: Lorenz
authors.initials: L
authors.lastname: Risch
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D017152:Antibodies, Antiphospholipid / Q000032:analysis*; D004912:Erythrocytes / Q000276:immunology; D006386:Hemagglutination Tests; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000032:analysis*; D016756:Immunoglobulins, Intravenous / Q000737:chemistry*; D007155:Immunologic Factors / Q000737:chemistry*; D007518:Isoantibodies / Q000032:analysis*; D009391:Nephelometry and Turbidimetry
chemical_list: D000017:ABO Blood-Group System; D017152:Antibodies, Antiphospholipid; D007147:Immunoglobulin Light Chains; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007518:Isoantibodies