Immune response to blood group antigens
Project leaders: Masja de Haas MD PhD, Barbera Veldhuisen PhD, and Prof Ellen van der Schoot MD PhD
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, 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 has been focused on the biochemical and molecular characterization of platelet antigens and in later years on the molecular characterization of red blood cell antigens, especially Rh. We now focus on new techniques for mass scale red cell genotyping and aim to unravel the molecular background of high-frequency red cell antigen systems. The ultimate goal of our research in this field 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 in 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.
Cost effective genotyping
In 2010 we have developed a genotyping assay in collaboration with MRC-Holland. The assay is based on the Multiplex Ligase Probe Amplification (MLPA) for 52 blood group antigens of 18 blood group systems (MNS, RH, LU, KEL, LE, FY, JK, DI, YT, SC, DO, CO, LW, GE, CROM, KN, IN and OK) and two platelet systems (HPA1 and HPA2). This assay is particularly useful for full genotyping of recipients, since also null alleles and variants (including >50 Rh variants) can be detected. For donor typing the fully automated ID-Core assay of Progenika which is based on our previously developed BloodChip is more suitable. The composition of this latter assay will be adapted to the requirements for Dutch blood banks.
Risk factors for alloimmunization
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). In 2010 we collected in collaboration with the blood bank in Amsterdam and investigators of the Netherlands Cancer Institute DNA from a control cohort of Dutch female blood donors.
In previous years we have developed several blood group genotyping assays (D, c, E, K) on cell free fetal (cff) DNA, and these assays are offered as a routine service since 7 years. In 2010 we evaluated their performance by comparing our test results with cord blood serology. Complete concordance was observed.
Key publications
- Veldhuisen B, Ligthart PC, Vidarsson G, Roels I, Folman CC, van der Schoot CE, de Haas M. Molecular analysis of the York antigen of the Knops blood group system. Transfusion 2011 Jul;51(7):1389-96.
- Grootkerk-Tax MG, Ait Soussan A, de Haas M, Maaskant-van Wijk PA, van der Schoot CE. Evaluation of prenatal RHD typing strategies on cell-free fetal DNA from maternal plasma. Transfusion 2006; 46(12):2142-8.
- Dohmen SE, Verhagen OJ, Muit J, Ligthart PC, van der Schoot CE. The restricted use of IGHV3 superspecies genes in anti-Rh is not limited to hyperimmunized anti-D donors. Transfusion 2006; 46(12):2162-8.
- Koelewijn JM, de Haas M, Vrijkotte TG, Bonsel GJ, van der Schoot CE. One single dose of 200 mug of antenatal RhIG halves the risk of anti-D immunization and hemolytic disease of the fetus and newborn in the next pregnancy. Transfusion 2008; 48(8):1721-1729.