Alloreactive T cells to Assess Acute Rejection Risk in Kidney Transplant Recipients. Issue 5 (20th April 2023)

• Record Type: Journal Article
• Authors: Mendoza Rojas, Aleixandra; Verhoeven, Jeroen G.H.P.; de Kuiper, Ronella; Clahsen-van Groningen, Marian C.; Boer, Karin; Hesselink, Dennis A.; van Gelder, Teun; van Besouw, Nicole M.; Baan, Carla C.
• Is Part Of: Transplantation direct. Volume 9:Issue 5(2023)
• Page Start: e1478
• Publication Date: 2023-04-20
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation -- Periodicals; 362.19795
• DOI: 10.1097/TXD.0000000000001478
• Languages: English
• ISSNs: 2373-8731

Abstract

Abstract : Background: Memory T cells are important mediators of transplant rejection but are not routinely measured before or after kidney transplantation. The aims of this study were as follows: (1) validate whether pretransplant donor-reactive memory T cells are reliable predictors of acute rejection (AR) (2) determine whether donor-reactive memory T cells can distinguish AR from other causes of transplant dysfunction. Methods: Samples from 103 consecutive kidney transplant recipients (2018–2019) were obtained pretransplantation and at time of for-cause biopsy sampling within 6 mo of transplantation. The number of donor-reactive interferon gamma (IFN-γ) and interleukin (IL)-21-producing memory T cells was analyzed by enzyme-linked immunosorbent spot (ELISPOT) assay. Results: Of the 63 patients who underwent a biopsy, 25 had a biopsy-proven acute rejection (BPAR; 22 aTCMR and 3 aAMR), 19 had a presumed rejection, and 19 had no rejection. Receiver operating characteristic analysis showed that the pretransplant IFN-γ ELISPOT assay distinguished between patients who later developed BPAR and patients who remained rejection-free (area under the curve [AUC] 0.73; sensitivity 96% and specificity 41%). Both the IFN-γ and IL-21 assays were able to discriminate BPAR from other causes of transplant dysfunction (AUC 0.81; sensitivity 87% and specificity 76% and AUC 0.81; sensitivity 93% and specificity 68%, respectively). Conclusions: This study validates that a high number of donor-reactive memory T cells before transplantation is associated with the development of AR after transplantation. Furthermore, it demonstrates that the IFN-γ and IL-21 ELISPOT assays are able to discriminate between patients with AR and patients without AR at the time of biopsy sampling.