Immune response to blood group antigens
The aim of this research line is to develop new diagnostic and preferentially also therapeutic options to further prevent and/or treat allo- or autoimmunization against blood cells. We are studying both the antigens (outlined below), which are the targets of the immune response, and the humoral immune response that leads to cell destruction.
Blood group antigens
In the past this research line focused on the biochemical and molecular characterization of platelet antigens. In later years the focus moved to the molecular characterization of red blood cell antigens, especially Rhesus (Rh). We now focus on new techniques for mass-scale red cell genotyping, and phenotyping, and aim to unravel the molecular background of high-frequency red cell antigen systems. The ultimate goal of our research is to change transfusion policy. At present, blood transfusion is only matched for ABO and RhD, and the donor is screened for the presence of red cell antibodies. By making available: 1) cost effective genotyping of both donors and recipients and 2) insight into risk factors for alloimmunization (genetic factors as well as disease-related), new algorithms for transfusion can be developed. Selected patient groups can be transfused with matched blood cell products. This will cause shifting from lab-based selection of blood products to electronic matching.
Ad 1) Using a Multiplex Ligase probe Amplification (MLPA) genotyping assay that we developed in collaboration with MRC-Holland, we are currently able to type 52 blood group antigens of 18 blood group systems and two platelet systems (HPA1 and HPA2). Since genotyping assays are hampered by relatively high costs and the presence of rare or even unknown null-alleles, we are currently also making an effort to set up unique proteomic-based and label-free assays for typing red blood cell antigens directly. In 2011 non-invasive fetal RhD typing was introduced in the Netherlands to guide both antenatal and postnatal anti-D prophylaxis in D-negative pregnant women. In the first year all cord blood samples are sent to Sanquin, and the program will be evaluated.
Ad 2) To identify genetic risk factors for alloimmunization, we are continuously banking DNA samples of red cell alloimmunized pregnant women for a genome-wide association study (GWAS). The implementation of samples is nearly finished and in collaboration with Prof Dr WH Ouwehand, Cambridge, over 2000 samples will be studied. The DNA bank of healthy Dutch donors (the Sanquin Control Cohort), which will serve as the control in our study, has already been used by several other GWAS projects and is available for research groups upon request.
- Scheffer PG, de Haas M, van der Schoot CE. The controversy about controls for fetal blood group genotyping by cell-free fetal DNA in maternal plasma. Curr Opin Hematol 2011; 18(6):467-73. Review.
- Vergeer M, Boekholdt SM, Sandhu MS, Ricketts SL, Wareham NJ, Brown MJ, de Faire U, Leander K, Gigante B, Kavousi M, Hofman A, Uitterlinden AG, van Duijn CM, Witteman JC, Jukema JW, Schadt EE, van der Schoot E, Kastelein JJ, Khaw KT, Dullaart RP, van Tol A, Trip MD, Dallinga-Thie GM. Genetic variation at the phospholipid transfer protein locus affects its activity and high-density lipoprotein size and is a novel marker of cardiovascular disease susceptibility. Circulation 2010; 122(5):470-77