IL-21 Positive Cells Predict Kidney Transplant Rejection Prior to Surgery

Since the demand for transplanted organs is much higher than the supply, predicting the likelihood of allograft survival following transplantation is important for effectively allocating the limited number of available organs, and scientists are continuously searching for improved methods of anticipating rejection. To this end, a team of scientists from the Netherlands sought to determine whether the levels of a particular subset of circulating donor-specific cells bearing the immune signaling molecule interleukin-21 (IL-21) could predict kidney transplant rejection.

Dr. Nicole van Besouw, Dr. Carla Baan, and their team pursued their hypothesis by analyzing patient samples in two separate studies. The first involved pre-transplant samples isolated from 35 patients, 15 of whom went on to experience early acute rejection following transplantation. The second assessed peripheral blood mononuclear cells (PBMCs) isolated from 46 patients 6 months after transplantation. 13 of these patients experienced late rejection.

The team found that patients that experienced early and late rejection events beared circulating donor-specific IL-21+ cells at significantly higher levels than patients that did not experience rejection.

In addition, particularly low levels of the cells were “associated with higher rejection-free survival,” suggesting that the cell population could be predictive of early and late rejection events and the survival time of the transplant.

Low levels of circulating donor-specific IL-21-producing cells were also associated with “the absence of anti-HLA antibodies,” proteins secreted by a type of white blood cell that are normally important to the rejection process.

The team published their findings in the scientific journal Frontiers in Immunology and suggest that treatment with anti-IL-21 monoclonal antibody could potentially one day be applied prophylactically to prevent acute T-cell mediated rejection (aTCMR) and acute antibody-mediated rejection (aABMR).

Keep in mind that, while it is exciting that the team demonstrated a role for these IL-21 positive cells in predicting kidney transplant rejection, their findings represent only those of one research group, and must be verified. The authors advise “a prospective validation study” and “an external multicentre validation.”

van Besouw NM, Yan L, de Kuiper R, et al. (2019) The Number of Donor-Specific IL-21 Producing Cells before and after Transplantation Predicts Kidney Graft Rejection. Frontiers in Immunology, 10: 748. doi: 10.3389/fimmu.2019.00748

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