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

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalClinical Biochemistry
Volume94
DOIs
Publication statusPublished - 1 Aug 2021

Bibliographical note

Funding Information:
The authors thank the staff of the medical library of the Faculty of Medicine, Chulalongkorn University, and the Erasmus MC Medical Library for providing the original and full-text articles used in this systematic review and meta-analysis. Suwasin Udomkarnjananun received a grant from King Chulalongkorn Memorial Hospital and the Thai Red Cross Society for conducting research at the Erasmus MC.

Funding Information:
Suwasin Udomkarnjananun received a grant from King Chulalongkorn Memorial Hospital and the Thai Red Cross Society for conducting research at the Erasmus MC.

Publisher Copyright:
© 2021 The Author(s)

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