Basaal I - P33 - High numbers of pre-transplant donor-specific IL-21 producing cells predicts acute rejection after kidney transplantation

N.M. van Besouw, R. de Kuiper, M.C. Clahsen-van Groningen, Y. Wu, J.N.M Ijzermans, D.A. Hesselink, C.C. Baan

Chair(s): dr. Ron W.F. de Bruin, Erasmus MC, Rotterdam

Thursday 10 march 2016

12:30 - 13:00h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)

Background:
IL-21 is a master regulator of function and homeostasis of the immune system. The major sources of IL-21 are CD4+ T-cells, including memory follicular T-helper cells and Th17 cells, as well as NKT cells and CD8+ T-cells. IL-21 can act in an autocrine fashion on these cell populations and on other cells (NK cells, B-cells, Tregs, DC and macrophages). Overproduction of IL-21 occurs in many inflammatory diseases such as rheumatoid arthritis, psoriasis and SLE. Because IL-21 supports the induction and expansion of the aggressive cytotoxic CD8+ T-cells, we questioned whether pre transplant IL-21 production can predict acute rejection after transplantation.

Methods:
The frequency of circulating IL-21 producing cells to donor cells was determined by Elispot assay in 17 patients before kidney transplantation: 10 patient with biopsy proven rejection (acute cellular rejection types 1 and 2), treated with high dose methylprednisolone, and 7 patients without rejection after transplantation. Stimulation with staphylococcal enterotoxin B (SEB) and a cocktail of peptides to influenza, CMV and EBV (ICE) served as positive control for the HLA class II and HLA I response, respectively.

Results:
Higher numbers of donor-specific IL-21 producing cells were found in the rejectors compared to non-rejectors (median 34/3x10E5 PBMC, range 16-70 vs. 6/3x10E5 PBMC, range 3-105; p=0.04). The frequency of IL-21 producing cells was significantly higher after SEB than after ICE stimulation (median 89/5x10E4 PBMC, range 11-504 vs. 2/3x10E5 PBMC, range 0-50; p=0.0002). No difference was found in frequency of IL-21 producing cells after SEB and ICE stimulation between the patient groups.

Conclusion:
IL-21 is mainly produced via an HLA class II restricted response. The production of pre transplant donor-specific IL-21 producing cells is linked to a high risk of acute rejection. Therefore, blocking IL-21 production may provide prevention of acute rejection.