Recombinant blood group proteins in clinical practice – from puzzling to binary antibody testing

Abstract

The main drawback of red blood cell (RBC)‐based antibody detection assays is that a positive reaction between serum and test cells does not identify the specificity of a given red blood cell antibody. When antibody mixtures or rare RBC antibodies are present, this indirect method reaches its limits. Recently, CE‐marked recombinant blood group proteins (rBGPs) have become available in sufficient quantity and quality. The advantage of rBGPs over RBCs is that proteins carrying a single antigen can be used in the antibody identification assay, so a positive test directly indicates the presence and specificity of the target antibody. The use of soluble rBGPs in addition to RBCs has been shown to increase the sensitivity and specificity of antibody detection and identification in cases with difficult‐to‐identify antibodies, resulting in increased efficiency in providing blood to immunized patients. The rBGPs have been successfully used in a wide range of solid‐phase assays (ELISA, microspheres, microarrays). Although all relevant antigen specificities have not yet been established, rBGPs have a diagnostic potential that could already be useful in antibody detection assays combining RBC‐derived antigens and recombinantly expressed antigens. Such combined assays would benefit from the potential of rBGPs for single‐step, direct antibody detection and identification, which could greatly facilitate and accelerate the identification of common and rare RBC antibodies. The clinical use of rBGPs in pretransfusion antibody screening would introduce a paradigm shift that could help to reduce the risk of haemolytic transfusion reaction, one of the leading causes of transfusion‐related death.