Sensitive HLA antibody testing and the risk of antibody-mediated rejection and graft failure

Tim Debyser; Jasper Callemeyn; Maarten Coemans; Johan Kerkhofs; Priyanka Koshy; Dirk Kuypers; Aleksandar Senev; Anat R. Tambur; Elisabet Van Loon; Karolien Wellekens; Maarten Naesens; Marie Paule Emonds

doi:10.1111/tan.15586

Sensitive HLA antibody testing and the risk of antibody-mediated rejection and graft failure

Tim Debyser, Jasper Callemeyn, Maarten Coemans, Johan Kerkhofs, Priyanka Koshy, Dirk Kuypers, Aleksandar Senev, Anat R. Tambur, Elisabet Van Loon, Karolien Wellekens, Maarten Naesens^*, Marie Paule Emonds

^*Corresponding author for this work

Surgery, Transplant Surgery Division

Research output: Contribution to journal › Article › peer-review

Abstract

Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex®) assays, which is more sensitive than the previously used enzyme-linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody-mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA- to Luminex-based testing. For this study, bio-banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre-existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow-up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex-based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA- to Luminex-based HLA testing was associated with a significant decrease in AMR occurrence post-transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex-based testing has the added value of preventing low-risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ.

Original language	English (US)
Article number	e15586
Journal	HLA
Volume	103
Issue number	6
DOIs	https://doi.org/10.1111/tan.15586
State	Published - Jun 2024

Funding

The authors gratefully express gratitude towards the centers of the Leuven Collaborative Group for Kidney Transplantation and all involved clinicians, nursing staff and patients. This work was supported by the Research Foundation \u2013 Flanders (FWO). KW, EVL and JC hold a FWO PhD fellowship grant. MC holds a FWO postdoctoral grant (). MN is supported by the FWO as a senior clinical investigator ( and ). 12D6423N 1844019N 1844024N The authors gratefully express gratitude towards the centers of the Leuven Collaborative Group for Kidney Transplantation and all involved clinicians, nursing staff and patients. This work was supported by the Research Foundation \u2013 Flanders (FWO). KW, EVL and JC hold a FWO PhD fellowship grant. MC holds a FWO postdoctoral grant (12D6423N). MN is supported by the FWO as a senior clinical investigator (1844019N and 1844024N).

Keywords

HLA antigens
graft rejection
histocompatibility testing
kidney transplantation

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Genetics

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10.1111/tan.15586

Cite this

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title = "Sensitive HLA antibody testing and the risk of antibody-mediated rejection and graft failure",

abstract = "Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex{\textregistered}) assays, which is more sensitive than the previously used enzyme-linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody-mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA- to Luminex-based testing. For this study, bio-banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre-existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow-up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex-based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA- to Luminex-based HLA testing was associated with a significant decrease in AMR occurrence post-transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex-based testing has the added value of preventing low-risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ.",

keywords = "HLA antigens, graft rejection, histocompatibility testing, kidney transplantation",

author = "Tim Debyser and Jasper Callemeyn and Maarten Coemans and Johan Kerkhofs and Priyanka Koshy and Dirk Kuypers and Aleksandar Senev and Tambur, {Anat R.} and {Van Loon}, Elisabet and Karolien Wellekens and Maarten Naesens and Emonds, {Marie Paule}",

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year = "2024",

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language = "English (US)",

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T1 - Sensitive HLA antibody testing and the risk of antibody-mediated rejection and graft failure

AU - Debyser, Tim

AU - Callemeyn, Jasper

AU - Coemans, Maarten

AU - Kerkhofs, Johan

AU - Koshy, Priyanka

AU - Kuypers, Dirk

AU - Senev, Aleksandar

AU - Tambur, Anat R.

AU - Van Loon, Elisabet

AU - Wellekens, Karolien

AU - Naesens, Maarten

AU - Emonds, Marie Paule

PY - 2024/6

Y1 - 2024/6

N2 - Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex®) assays, which is more sensitive than the previously used enzyme-linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody-mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA- to Luminex-based testing. For this study, bio-banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre-existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow-up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex-based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA- to Luminex-based HLA testing was associated with a significant decrease in AMR occurrence post-transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex-based testing has the added value of preventing low-risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ.

AB - Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex®) assays, which is more sensitive than the previously used enzyme-linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody-mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA- to Luminex-based testing. For this study, bio-banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre-existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow-up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex-based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA- to Luminex-based HLA testing was associated with a significant decrease in AMR occurrence post-transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex-based testing has the added value of preventing low-risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ.

KW - HLA antigens

KW - graft rejection

KW - histocompatibility testing

KW - kidney transplantation

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Sensitive HLA antibody testing and the risk of antibody-mediated rejection and graft failure

Abstract

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Keywords

ASJC Scopus subject areas

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