Alloreactive T cells to Assess Acute Rejection Risk in Kidney Transplant Recipients

Autor: Aleixandra Mendoza Rojas, MSc, Jeroen G.H.P. Verhoeven, MD, Ronella de Kuiper, BSc, Marian C. Clahsen-van Groningen, MD, PhD, Karin Boer, PhD, Dennis A. Hesselink, MD, PhD, Teun van Gelder, MD, PhD, Nicole M. van Besouw, PhD, Carla C. Baan, PhD
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Transplantation Direct, Vol 9, Iss 5, p e1478 (2023)
Druh dokumentu: article
ISSN: 2373-8731
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DOI: 10.1097/TXD.0000000000001478
Popis: 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.
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