Donor-specific ELISPOT assay for predicting acute rejection and allograft function after kidney transplantation: A systematic review and meta-analysis

Suwasin Udomkarnjananun,Stephen J Kerr,Natavudh Townamchai,Nicole M Van Besouw,Dennis A Hesselink,Carla C Baan

doi:10.1016/j.clinbiochem.2021.04.011

Abstract

Acute rejection remains an important problem after kidney transplantation. Enzyme-linked immunosorbent spot (ELISPOT) assay has been investigated extensively and has shown promising results as a predictor of allograft rejection. The objective of this study was to systematically review and analyze the predictive value of the donor-specific ELISPOT assay to identify recipients at risk for acute rejection. Electronic databases were searched for studies reporting donor-specific ELISPOT and kidney transplantation outcomes. Odds ratio (OR) for acute rejection was calculated, along with standardized mean difference (SMD) of cytokine producing-cells between recipients with and without acute rejection. Pooled estimates were calculated using random-effect models. The positive ELISPOT cutoff frequencies were extracted from each study. From 665 articles found, 32 studies were included in the meta-analysis. IFN-γ was the most investigated cytokine (30 out of 32 studies). Patients with positive pre-transplantation donor-reactive IFN-γ ELISPOT had an OR of 3.3 for acute rejection (95%-CI 2.1 to 5.1), and OR of 6.8 (95%-CI 2.5 to 18.9) for post-transplantation ELISPOT. Recipients with rejection had significantly higher frequencies of pre- and post-transplantation cytokine producing-cells (SMD 0.47, 95%-CI 0.07 to 0.87 and SMD 3.68, 95%-CI 1.04 to 6.32, respectively). Pre-transplantation ELISPOT had a positive predictive value of 43% and a negative predictive value of 81% for acute rejection. A positive ELISPOT result was associated with a lower estimated glomerular filtration rate (SMD −0.59, 95%-CI −0.83 to −0.34). In conclusion, patients with a high frequency of donor-reactive IFN-γ ELISPOT are at higher risk for acute rejection. The donor-specific IFN-γ ELISPOT assay can serve as an immune-monitoring tool in kidney transplantation.

Highlights

Acute kidney transplant rejection remains a major barrier to allograft longevity [1,2,3]
The exact timing of the post-transplantation Enzyme-linked immunosorbent spot (ELISPOT) measurements varied between studies, ranging from an exact time point in the first few months after transplantation, whereas in other studies, the ELISPOT assay was measured at non-fixed time points
The results of this systematic review and meta-analysis demonstrate that ELISPOT is a useful immune-monitoring tool that can assist clini cians in stratifying the risk for acute rejection

Summary

Introduction

Acute kidney transplant rejection remains a major barrier to allograft longevity [1,2,3]. With improvements in immunosuppressive treatment, the incidence of acute rejection in the first year after transplantation has decreased to 10–20%, depending on the recipient’s immunological risk [2,4,5,6]. Patients with a highimmunological risk profile could receive more potent immunosuppres sion, for example with T lymphocyte-depleting agents, whereas patients with a low risk of rejection could be given standard or less intense immunosuppression. This would prevent over-immunosuppression and may reduce complications such as malignancy and infection [8,9]

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Conclusion