Graft failure is the fear of every transplant patient. A possible form of rejection is ABMR (antibody-mediated rejection), which can occur early or late after transplantation. Cross-matching and risk assessment prior to transplantation can reasonably prevent ABMR at an early stage. However, late-stage AMBR is a major cause of graft failure despite maintenance immunosuppression.
Approximately twenty percent of transplant patients experience this chronic rejection, which at that point there is actually nothing more that can be done about it. Harry van Goor, professor of experimental nephropathology: ”If a transplanted patient has ABMR early after transplantation, we try to filter out the antibodies. In the late phase after transplantation, there is often too much inflammation and scarring in the kidney. The protein loss can therefore become increasingly worse, resulting in the kidney breaking down. The patient then has to go on dialysis or needs a new kidney and you really want to prevent that. With this subsidy application we want to see ABMR arrive at an earlier time.”
In the period immediately after the transplant, doctors have a reasonable insight into the cause of rejection. Patients with a rejection reaction in the early phase produce antibodies directed against HLA. But in the case of rejection in the chronic phase, it is not always known which antibodies are the cause. Antibodies against HLA also play a role in the long term, but they cannot explain everything. So there must be something else, a process that is not yet fully known.
In their research, Van Goor and co-applicant nephrologist Jan-Stephan Sanders use a recent, innovative method (PhIP-Seq) to gain insight into relevant antibodies. The big advantage is that the technique can image half a million antibodies in the blood at once, while previously researchers could only look at that one antibody that was suspected of playing a role in a specific disease. So not only the antibodies directed against the donor organ are imaged, but also those against bacteria, viruses or allergens. Van Goor: “Interesting findings have been revealed using this technique in other studies.”
The researchers use the TransplantLines biobank of the UMCG, containing biomaterials from 1,400 transplant patients and donors. They will compare fifty patients with ABMR with fifty patients without ABMR and use 50 kidney donors as a control group.
Van Goor: ”We hope to gain innovative insight with this research. If we find some antibodies, we can investigate whether they are present earlier in the process, so that we can identify a chronic rejection reaction earlier. This also allows us to intervene earlier. After all, every patient with a donor kidney receives immune system suppressors. By increasing this, you can inhibit or perhaps prevent AMBR. ”As a doctor you can also intervene in other areas, but the most important are anti-rejection medicines. That’s actually a simple treatment.”
Van Goor and Sanders will receive a Creativity grant from the Kolff subsidy program to conduct this research.