The Assesment of Pre-transplant Donor-reactive IL-21 Producing T Cells as a Tool to Identify Patients at Risk for Acute Rejection

A. Mendoza Rojas¹, T. van Gelder², R. de Kuiper¹, D. Reijerkerk¹, M. C. Clahsen-van Groningen³, D. A. Hesselink¹, C. C. Baan¹, N. M. van Besouw¹

¹Internal Medicine, Neprology & Transplantation, Erasmus Medical Center, Rotterdam, Netherlands, ²Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, Netherlands, ³Internal Medicine, Pathology, Erasmus Medical Center, Rotterdam, Netherlands

Meeting: 2021 American Transplant Congress

Abstract number: 651

Keywords: Kidney transplantation, Panel reactive antibodies, Rejection, T cell reactivity

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: The measurement of panel-reactive antibodies (PRA) has proven valuable in the transplant setting but it does not account for the presence of donor-reactive memory T cells. Previous studies have shown that these cells are associated with the development of acute rejection. The aim of this study, was to assess whether pre-transplant memory T and B cell alloreactivity are associated with increased rejection risk of kidney transplant recipients.

*Methods: Peripheral blood mononuclear cell (PBMC) samples from 114 kidney transplant recipients (transplanted between 2010-2013) were obtained pre-transplantation. The number of donor-reactive IL-21 (cytokine known to provide help to B cells) producing T cells was analyzed by enzyme-linked immunospot assay (Elispot). Patient cells were stimulated with irradiated donor cells. Historical PRA and/or the presence of serum anti-HLA antibodies were used to determine the presence of B cell alloreactivity before transplantation.

*Results: A total of 30 patients developed acute rejection within 6 months after transplantation. Pre-transplant B cell alloreactivity was present in 16/30 (53%) patients with rejection and 33/84 (39%) patients with no rejection. The number of donor-reactive IL-21 producing T cells was significantly higher in patients with rejection (p=0.03). A ROC curve to assess the reliability of donor-reactive IL-21 producing T cells in predicting rejection, resulted in an AUC of 0.638 with a sensitivity of 0.63 and specificity of 0.60 (PPV: 21.5% and NPV: 90.1%). Multivariate binary logistic regression showed that donor age (OR: 1.057, 95% CI 1.017- 1.098) and number of donor-reactive IL-21 producing T cells (OR 1.015, 95% CI 1.003- 1.026) were indicators of an increased risk for the development of rejection (p=0.008).

*Conclusions: The number of pre-transplant donor-reactive IL-21 producing T-cells is an independent predictor for the development of acute rejection within the first 6 months after kidney transplantation. In contrast, pre-transplant B cell alloreactivity was not significantly related to incidence of rejection. Our data form a good starting point for research into the added value of monitoring pre-transplant donor-reactive IL-21 producing T-cells for assessment of immunological risk.

To cite this abstract in AMA style:

Rojas AMendoza, Gelder Tvan, Kuiper Rde, Reijerkerk D, Groningen MCClahsen-van, Hesselink DA, Baan CC, Besouw NMvan. The Assesment of Pre-transplant Donor-reactive IL-21 Producing T Cells as a Tool to Identify Patients at Risk for Acute Rejection [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/the-assesment-of-pre-transplant-donor-reactive-il-21-producing-t-cells-as-a-tool-to-identify-patients-at-risk-for-acute-rejection/. Accessed May 16, 2025.

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