Failure to remove de novo donor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss – a retrospective study

Michela Cioni, Arcangelo Nocera, Augusto Tagliamacco, Sabrina Basso, Annalisa Innocente, Iris Fontana, Alberto Magnasco, Antonella Trivelli, Catherine Klersy, Antonella Gurrado, Miriam Ramondetta, Stella Boghen, Laura Catenacci, Enrico Verrina, Giacomo Garibotto, Gian Marco Ghiggeri, Massimo Cardillo, Fabrizio Ginevri, Patrizia Comoli

Research output: Contribution to journalArticle

Abstract

Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative % eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow-up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P < 0.001) and presence of C3d-binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti-humoral treatment. In the multivariable analysis, C3d-binding ability (P < 0.05), but not C1q-binding, and high mean fluorescence intensity (P < 0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high-MFI DSAs.

Original languageEnglish
JournalTransplant International
DOIs
Publication statusAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Retrospective Studies
Tissue Donors
Transplants
Kidney
Antibodies
Intravenous Immunoglobulins
Treatment Failure
Therapeutics
Plasmapheresis
Graft Survival
Allografts
Fluorescence
Pediatrics
Research
Rituximab

Keywords

  • anti-humoral therapy
  • antibody-mediated rejection
  • complement-binding DSA
  • de novo donor-specific anti-HLA antibodies
  • pediatric kidney transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

@article{6f963c441ed14f75b3414819019f00a9,
title = "Failure to remove de novo donor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss – a retrospective study",
abstract = "Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative {\%} eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow-up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P < 0.001) and presence of C3d-binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti-humoral treatment. In the multivariable analysis, C3d-binding ability (P < 0.05), but not C1q-binding, and high mean fluorescence intensity (P < 0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high-MFI DSAs.",
keywords = "anti-humoral therapy, antibody-mediated rejection, complement-binding DSA, de novo donor-specific anti-HLA antibodies, pediatric kidney transplantation",
author = "Michela Cioni and Arcangelo Nocera and Augusto Tagliamacco and Sabrina Basso and Annalisa Innocente and Iris Fontana and Alberto Magnasco and Antonella Trivelli and Catherine Klersy and Antonella Gurrado and Miriam Ramondetta and Stella Boghen and Laura Catenacci and Enrico Verrina and Giacomo Garibotto and Ghiggeri, {Gian Marco} and Massimo Cardillo and Fabrizio Ginevri and Patrizia Comoli",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/tri.13325",
language = "English",
journal = "Transplant International",
issn = "0934-0874",
publisher = "Blackwell Publishing Ltd",

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TY - JOUR

T1 - Failure to remove de novo donor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss – a retrospective study

AU - Cioni, Michela

AU - Nocera, Arcangelo

AU - Tagliamacco, Augusto

AU - Basso, Sabrina

AU - Innocente, Annalisa

AU - Fontana, Iris

AU - Magnasco, Alberto

AU - Trivelli, Antonella

AU - Klersy, Catherine

AU - Gurrado, Antonella

AU - Ramondetta, Miriam

AU - Boghen, Stella

AU - Catenacci, Laura

AU - Verrina, Enrico

AU - Garibotto, Giacomo

AU - Ghiggeri, Gian Marco

AU - Cardillo, Massimo

AU - Ginevri, Fabrizio

AU - Comoli, Patrizia

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative % eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow-up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P < 0.001) and presence of C3d-binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti-humoral treatment. In the multivariable analysis, C3d-binding ability (P < 0.05), but not C1q-binding, and high mean fluorescence intensity (P < 0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high-MFI DSAs.

AB - Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative % eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow-up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P < 0.001) and presence of C3d-binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti-humoral treatment. In the multivariable analysis, C3d-binding ability (P < 0.05), but not C1q-binding, and high mean fluorescence intensity (P < 0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high-MFI DSAs.

KW - anti-humoral therapy

KW - antibody-mediated rejection

KW - complement-binding DSA

KW - de novo donor-specific anti-HLA antibodies

KW - pediatric kidney transplantation

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