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Preformed donor‐reactive T cells that persist after ABO desensitization predict severe T cell‐mediated rejection after living donor kidney transplantation – a retrospective study


Schachtner, Thomas; Stein, Maik; Otto, Natalie M; Reinke, Petra (2020). Preformed donor‐reactive T cells that persist after ABO desensitization predict severe T cell‐mediated rejection after living donor kidney transplantation – a retrospective study. Transplant International, 33(3):288-297.

Abstract

Preformed donor‐reactive T cells are relatively resistant to standard immunosuppression and account for an increased incidence of T cell‐mediated rejection (TCMR) and inferior kidney allograft outcomes. We analyzed 150 living donor kidney transplant recipients (KTRs) of a first kidney allograft. Ninety‐eight ABO‐compatible (ABOc) and 52 ABO‐incompatible (ABOi) KTRs were included. Samples were collected at 6 time points, before rituximab, before immunoadsorption and pretransplantation, at +1, +2, and +3 months posttransplantation, and donor‐reactive T cells were measured by interferon‐γ ELISPOT assay. Twenty of 98 ABOc (20%) and 12 of 52 ABOi KTRs (23%) showed positive pretransplant ELISPOT. Eight of 20 ABOc‐KTRs (40%) with positive pretransplant ELISPOT showed TCMR, whereas 17 of 78 ABOc‐KTRs (22%) with negative pretransplant ELISPOT did (P = 0.148). Seven of 12 ABOi KTRs (57%) with positive pretransplant ELISPOT showed TCMR, whereas only 3 of 40 ABOi KTRs (8%) with negative pretransplant ELISPOT did (P < 0.001). Interestingly, 6 of 7 ABOi KTRs with positive pretransplant ELISPOT that persists after ABO desensitization developed TCMR. Among 118 KTRs with negative pretransplant ELISPOT, 10 of 72 ABOc‐KTRs (14%), but 0 of 46 ABOi KTRs, developed positive posttransplant ELISPOT (P = 0.006). Preformed donor‐reactive T cells that persist despite ABO desensitization identify KTRs at highest risk of TCMR. Less de‐novo donor‐reactive T cells after ABO desensitization may account for less TCMR. Both, the use of rituximab and early initiation of calcineurin inhibitor‐based maintenance immunosuppression may contribute to these findings.

Abstract

Preformed donor‐reactive T cells are relatively resistant to standard immunosuppression and account for an increased incidence of T cell‐mediated rejection (TCMR) and inferior kidney allograft outcomes. We analyzed 150 living donor kidney transplant recipients (KTRs) of a first kidney allograft. Ninety‐eight ABO‐compatible (ABOc) and 52 ABO‐incompatible (ABOi) KTRs were included. Samples were collected at 6 time points, before rituximab, before immunoadsorption and pretransplantation, at +1, +2, and +3 months posttransplantation, and donor‐reactive T cells were measured by interferon‐γ ELISPOT assay. Twenty of 98 ABOc (20%) and 12 of 52 ABOi KTRs (23%) showed positive pretransplant ELISPOT. Eight of 20 ABOc‐KTRs (40%) with positive pretransplant ELISPOT showed TCMR, whereas 17 of 78 ABOc‐KTRs (22%) with negative pretransplant ELISPOT did (P = 0.148). Seven of 12 ABOi KTRs (57%) with positive pretransplant ELISPOT showed TCMR, whereas only 3 of 40 ABOi KTRs (8%) with negative pretransplant ELISPOT did (P < 0.001). Interestingly, 6 of 7 ABOi KTRs with positive pretransplant ELISPOT that persists after ABO desensitization developed TCMR. Among 118 KTRs with negative pretransplant ELISPOT, 10 of 72 ABOc‐KTRs (14%), but 0 of 46 ABOi KTRs, developed positive posttransplant ELISPOT (P = 0.006). Preformed donor‐reactive T cells that persist despite ABO desensitization identify KTRs at highest risk of TCMR. Less de‐novo donor‐reactive T cells after ABO desensitization may account for less TCMR. Both, the use of rituximab and early initiation of calcineurin inhibitor‐based maintenance immunosuppression may contribute to these findings.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Transplantation
Uncontrolled Keywords:Transplantation
Language:English
Date:1 March 2020
Deposited On:10 Feb 2021 11:13
Last Modified:11 Feb 2021 21:00
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0934-0874
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/tri.13551
PubMed ID:31696547

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