Universal red blood cells--enzymatic conversion of blood group A and B antigens.
Accidental transfusion of ABO-incompatible red blood cells (RBCs) is a leading cause of fatal transfusion reactions. To prevent this and to create a universal blood supply, the idea of converting blood group A and B antigens to H using specific exo-glycosidases capable of removing the immunodominant sugar residues was pioneered by Goldstein and colleagues at the New York Blood Center in the early 1980s. Conversion of group B RBCs to O was initially carried out with alpha-galactosidase extracted from coffee beans. These enzyme-converted O (ECO) RBCs appeared to survive normally in all recipients independent of blood group. The clinical trials moved from small infusions to single RBC units and finally multiple and repeated transfusions. A successful phase II trial utilizing recombinant enzyme was reported by Kruskall and colleagues in 2000. Enzymatic conversion of group A RBCs has lagged behind due to lack of appropriate glycosidases and the more complex nature of A antigens. Identification of novel bacterial glycosidases with improved kinetic properties and specificities for the A and B antigens has greatly advanced the field. Conversion of group A RBCs can be achieved with improved glycosidases and the conversion conditions for both A and B antigens optimized to use more cost-efficient quantities of enzymes and gentler conditions including neutral pH and short incubation times at room temperature. Of the different strategies envisioned to create a universal blood supply, the ECO concept is the only one, for which human clinical trials have been performed. This paper discusses some biochemical and clinical aspects of this developing technology.
Department of Transfusion Medicine, Institution of Laboratory Medicine, Lund University and Blood Center, University Hospital, 221 85 Lund, Sweden. Martin_L.Olsson@transfumed.lu.se
Martin L
ML
Olsson
Cheryl A
CA
Hill
Humberto
H
de la Vega
Qiyong P
QP
Liu
Mark R
MR
Stroud
Jean
J
Valdinocci
Steven
S
Moon
Henrik
H
Clausen
Margot S
MS
Kruskall
D000017:ABO Blood-Group System; D001426:Bacterial Proteins / Q000494:pharmacology; D001787:Blood Group Incompatibility / Q000517:prevention & control*; D001788:Blood Grouping and Crossmatching; D002986:Clinical Trials as Topic; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000276:immunology*; D005544:Forecasting; D005656:Fungal Proteins / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000494:pharmacology*; D006801:Humans; D007519:Isoantigens / Q000187:drug effects* / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism*; D025942:Oligosaccharides, Branched-Chain; D013379:Substrate Specificity; D065227:Transfusion Reaction; D014312:Trisaccharides / Q000378:metabolism*
D000017:ABO Blood-Group System; D001426:Bacterial Proteins; D005656:Fungal Proteins; D007519:Isoantigens; D009844:Oligosaccharides; D025942:Oligosaccharides, Branched-Chain; D014312:Trisaccharides; C101335:blood group A trisaccharide; C406478:blood group B trisaccharide; D006026:Glycoside Hydrolases