Uncensored immune profiling in kidney transplantation: towards individualized immunosuppressive treatment

E.G. Kamburova, R.L. Smeets, W.B.L. Alkema, I. Joosten, L.B. Hilbrands, H. Koenen, M.C. Baas

Wednesday 4 march 2020

14:00 - 14:10h at Joep Nicolas zaal

Parallel session: Parallel sessie IV – Basale abstracts

Background: The favorable effects of more powerful immunosuppressive drugs (ISD) on patient and graft survival is accompanied by side effects such as infections and cancer. Until now we are not able to determine the minimal intensity of immunosuppressive therapy that is required for an individual renal transplant recipient (RTR). The aim of this study is to identify RTR who are eligible to lower doses of ISD without the risk of infection.

Methods: We analyze 10 patients with recurrent non-melanoma skin cancer (NMSC) at least 10 years after transplantation hypothesized to have clinically ‘weak/quiet’ immune status versus 10 matched patients without NMCS who potentially have a ‘strong/responsive’ immune status. Furthermore we include 20 pretransplant end-stage renal disease patients and 10 age-matched healthy controls. 20 ml blood is drawn and samples are analyzed within hours after collection. Flow cytometry is performed on whole blood and isolated PBMC’s using 6 standardized 10 color panels, resulting in over 200 different leukocyte subsets. Additionally, PBMC’s are stimulated for 30 minutes with pathway specific stimuli to induce ex vivo phosphorylation of various intracellular pathways. The combined data of the leukocyte subsets and the dynamic profile determined by the phosphorylation changes are expected to yield discriminative personalized profiles. Using different unsupervised multivariate analyses we will determine whether the immune status of NMSC patients is different from those without NMSC and how this differs from pretransplant patients and HC.

Results: The preliminary results of this novel technique are promising. We already are able to discriminate the personalized profiles of patients long after transplantation versus pretransplant patients, and versus healthy controls. Individual profiles of the patients in the different subgroups are now analyzed. After inclusion and analysis are finished in February 2020 we will present the detailed data of all subgroups at the Boot-conference in March.

Conclusions: Our data suggest that a personalized immune signature can be identified by uncensored analysis of whole blood and PBMCs of renal transplant patients. This would help to avoid morbidity and mortality associated with over- and underimmunosuppression. Applying this method for the analysis of the immune system of RTR is a wholly new approach in the transplant field.