Lymphocyte immunotherapy (LIT) as a model system to predict humoral alloimmunity in transplantation: Validation of the Cambridge HLA immunogenicity algorithm

• Applicant: Professor Dr. Dietrich Kabelitz
• Subject Area: Immunology ; Hematology, Oncology
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 335741949

HLA compatibility between recipient and donor is a key factor for success in organ transplantation. Preformed HLA antibodies can induce acute rejection, and newly formed antibodies after organ transplantation can reduce organ function and success rates. HLA compatibility is determined by HLA genotyping, but immunogenicity of HLA molecules is determined by their three-dimensional structure. Since more than 20 years, lymphocyte immunotherapy (LIT) is performed at the Institute of Immunology, Kiel University, in couples suffering from recurrent embryo implantation failure in in-vitro fertilization programmes, after careful exclusion of all other possible factors. The woman is immunized intradermally with partners peripheral blood lymphocytes. After 4 weeks, anti-HLA antibodies are detectable in the serum as a surrogate marker of immunization. We have thus available a worldwide unique cohort of sera from otherwise healthy individuals before and after allo-immunization and in a precisely known HLA setting. In contrast to organ transplantation, there is no influence of immunosuppressive medication, and we can thus determine the immunogenicity of individual HLA alleles against the HLA background of the immunized woman. In a previous study we provided HLA typing and HLA-antibody results from 191 LIT couples to our collaboration partner Dr. Kosmoliaptsis (Cambridge) who has developed the Cambridge HLA immunogenicity algorithm based on the HLA phenotypes of mostly causasian population. In the frame of the currently applied project we would like to include 100 more couples from our LIT cohort, of which at least one (or both) are not of German, Polnish, Scandinavian or Russian descent. Pre- and post-LIT as well as DNA is available. Both partners will be HLA typed (high resolution), and antibodies in pre- and post-LIT sera will be analyzed and specified by Luminex technology. Results will be transferred to Dr. Kosmoliaptsis for integration into the Cambridge HLA immunogenicity algorithm. We anticipate that the inclusion of less frequent HLA alleles will make the algorithm even more suitable. Overall, the long-term goal is to include the Cambridge HLA immunogenicity algorithm into national and international organ allocation systems (Eurotransplant).

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Cooperation Partner: Dr. Vasilis Kosmoliaptsis