Transplant Diagnostics
Transplantation diagnostics focus on histocompatibility and immunogenetics in the context of organ transplantation and hematopoietic stem cell transplantation. HLA antigen determination, HLA antibody screening and HLA antibody differentiation are the basis for all transplantations to ensure donor-recipient compatibility. Transplant-related diagnostics are strictly regulated by the Transplantation Act, guidelines of the German Medical Association, standards of the Eurotransplant Foundation, the European Federation for Immunogenetics, the German Foundation for Organ Transplantation and the Central Bone Marrow Donor Registry Germany
The basis of organ and stem cell transplantation is the definition of the tissue markers of the recipient and the prospective donor. In addition to the determination of the ABO blood group, the characterization of the HLA antigens plays an important role. Due to the considerable polymorphism of the genes underlying the HLA complex, more than 24,000 alleles can currently be differentiated at the transplantation-relevant HLA gene sites A, B, C, DRB1, DQB1 and DPB1. In addition, the characterization of other tissue characteristics (e.g. MICA, KIR, HA-1) may be required for specific questions.
In order to achieve maximum precision, antigen determination is performed exclusively by molecular genetic methods, predominantly by direct sequencing or Next Generation Sequencing. Depending on the number and coupling of the polymorphisms examined, different degrees of resolution of an HLA antigen profiling are distinguishable. The more detailed information is obtained from the DNA. the higher the degree of resolution in an HLA antigen profiling. Low resolution HLA antigen profiling is often sufficient for organ transplantation, whereas the highest resolution level is usually required for the transplantation of hematopoietic stem cells. In addition, the related stem cell donation often requires a complete haplotype segregation analysis.
Antibody diagnostics involves the exclusion or detection of antibodies against HLA and non-HLA antigens as well as prospective in vitro compatibility testing between recipient and donor (cross match). A distinction is made between immune screening and immune monitoring.
Immune Screening
The immune screening comprises the detection and, if necessary, specification of HLA and non-HLA antibodies prior to transplantation. This analysis is performed regularly in patients prior to organ transplantation and in patients prior to stem cell transplantation if a mismatch is present in one of the genes relevant for stem cell transplantation (HLA-A, B, C, DRB1, DQB1, DPB1). In patients on the kidney transplant waiting list, immune screening is performed regularly every three months (quarterly screening) to ensure accelerated organ allocation.
Immune Monitoring
The immune monitoring is performed for patients after organ transplantation. The purpose of this monitoring is to detect HLA antibodies specifically directed against donor HLA antigens (Donor Specific Antibodies - DSA). The detection and course of DSA is crucial for the therapy of humoral rejection and thus for the function and survival of the transplant.
The Register Donor Search Unit has the task of immediately identifying an HLA-compatible unrelated stem cell donor for patients requiring a blood stem cell transplant (bone marrow or peripheral blood stem cell transplant) if no related stem cell donor is available. A donor is considered identical if at least one high-resolution identity exists for the genes HLA-A, B, C, DRB1, DQB1. More than nine million registered stem cell donors are currently available worldwide for this purpose.