Around 20 percent of donor kidneys are no longer functional five years after transplantation. This is usually due to a rejection reaction. How can more rejections be prevented and donor organs saved? The measurement of molecular markers opens up new perspectives for this: a test system detects rejection reactions earlier and more accurately and enables timely and more differentiated therapy. Dr. Dr. Gunilla Einecke, Senior Physician at the Clinical Department of Nephrology and Hypertension at Hannover Medical School (MHH), was awarded the Rudolf Pichlmayr Prize 2019 by the German Transplantation Society for her scientific work on the "molecular microscope".

Donor organs challenge the recipient's immune system with their foreign proteins (antigens) to trigger an immune response. The tissue is attacked and, in the worst case, destroyed. In return, the recipient produces immune cells, some of which in turn release destructive antibodies. In order to recognize and stop immune reactions in good time, tissue samples are taken from the donor organ after transplantation and examined by pathologists under a conventional optical microscope. If there is a rejection reaction, the dose of medication to suppress the immune system (immunosuppressants), which is taken permanently by transplanted patients, is increased or other medication is used.

Tissue diagnostics in pathology is the gold standard

"For rejection diagnostics, there is still no way to do without conventional tissue examination. It is the gold standard," says Dr. Einecke. However, it only shows the consequences of immune reactions in the tissue, but not their onset and mechanism. In addition, the quality of the pathological examination depends on the individual expertise of the pathologist and the result cannot be quantified.

Gene activities, on the other hand, can be measured precisely. The more active a gene is, the more messenger RNA it produces. With the help of gene patterns, the rejection reactions in the tissue can be typified and their risk assessed. And treatment with immunosuppressive drugs can be adjusted accordingly, as studies in animal models and on tissue material from transplanted patients have shown. Dr. Einecke and her scientific cooperation partners at the Canadian University of Edmonton have determined which genes are active in early and late rejection reactions involving different immune cell types.

Clinical study investigates the informative value of the "molecular microscope"

Tissue samples from the donor organ must also be used for the "Molecular Microscope". The "Molecular Microscope Diagnostic SystemR" test system is already commercially available and in clinical use internationally. In Germany, it is only used in clinical studies. "We are currently investigating how microscopic and molecular tissue diagnostics correlate with disease development and response to therapy in patients in a large international study involving several centers," says Dr. Einecke. Algorithms can be used to calculate risks and develop recommendations for therapy to ensure the long-term survival of donor organs.

Prize in memory of MHH transplant physician Rudolf Pichlmayr

The Rudolf Pichlmayr Prize of the German Transplantation Society (DTG) commemorates the transplant surgeon Prof. Dr. Rudolf Pichlmayr (1932-1997), Hannover Medical School, who had a lasting influence on transplant medicine in Germany. The prize is awarded at the annual conference of the DTG for outstanding achievements in transplantation medicine. The prize money amounts to EUR 10,000 and is donated by Biotest AG.