In kidney transplantation, HLA matching between donor and recipient is beneficial for graft survival. However, many recipients receive an HLA mismatched graft, potentially leading to development of donor-specific antibodies (DSA). However, not every HLA antigen mismatch induces an alloimmune response. This is due to polymorphic amino acid configurations, often referred to as epitopes, on HLA molecules. While each HLA antigen consist of a unique set of epitopes, an individual epitope can be shared by multiple HLA antigens. Thus, the optimal donor can theoretically be selected by avoiding immunogenic epitope mismatches.
Therefore, one of my research project focusses on the definition of immunogenic epitopes. For this purpose, we have developed the software program HLA-EMMA, that performs compatibility analysis between donor and recipient on the amino acid level. Currently, we are working on a large cohort study to identify amino acid mismatches associated with DSA development, which is part of the 18th International HLA & immunogenetics workshop.
Additionally, we are generating recombinant human HLA class II monoclonal antibodies (mAbs). Analysis of their reactivity patterns leads to identification of amino acids involved in antibody binding, including amino acids that can be immunogenic. These mAbs will also contribute to the understanding of the antigenicity of HLA antibodies. As the presence of HLA antibodies complicates finding a suitable donor for transplantation, this will contribute in defining acceptable and unacceptable HLA epitopes to predict a negative crossmatch.
After finishing my master’s in Molecular Life Science at the Radboud University in Nijmegen, I started my PhD in transplantation immunology under the supervision of Frans Claas, Sebastiaan Heidt, and Dave Roelen at the department of Immunohematology and Blood Transfusion of the LUMC. In 2020, I successfully defended my thesis “Towards HLA epitope matching in clinical transplantation” at the Leiden University. Since 2020, I am working as a postdoctoral researcher in the transplant immunology group in the department of Immunology. The focus of my research is the definition of immunogenic epitopes and the generation and characterization of human recombinant monoclonal HLA class II antibodies.
Generation and reactivity analysis of human recombinant monoclonal antibodies directed against epitopes on HLA-DR
Kramer C.S.M., Franke-van Dijk M.E.I., Bakker K.H., Uyar-Mercankaya M., Karahan G.E., Roelen D.L., Claas F.H.J., Heidt S.
American Journal of transplantation 2020 Online ahead of print
HLA-EMMA: a user-friendly tool to analyse HLA class I and class II compatibility on amino acid level
Kramer CSM, Koster J, Haasnoot GW, Roelen DL, Claas FHJ, Heidt S.
Recombinant human monoclonal HLA antibodies of different IgG subclasses recognising the same epitope: Excellent tool to study differential effects of donor-specific antibodies
Kramer CSM, Franke-van Dijk MEI, Priddey AJ, Pongrács T, Zilvold-van den Oever CCC, Rademaker HJ, de Haan N, Wuhrer M, Kosmoliaptsis V, Parren PWHI, Mulder A, Roelen DL, Claas FHJ, Heidt S.