Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome

The consolidation of single antigen beads (SAB-panIgG) assay in the detection of preformed anti-human leukocyte antigen (HLA) antibodies has improved transplantation success. However, its high sensitivity has limited the allograft allocation for sensitized patients, increasing their waiting time. A...

Full description

Bibliographic Details
Main Authors: Juan Molina, Ana Navas, María-Luisa Agüera, Cristian Rodelo-Haad, Corona Alonso, Alberto Rodríguez-Benot, Pedro Aljama, Rafael Solana
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.01310/full
_version_ 1811256052805533696
author Juan Molina
Ana Navas
María-Luisa Agüera
María-Luisa Agüera
Cristian Rodelo-Haad
Corona Alonso
Corona Alonso
Alberto Rodríguez-Benot
Alberto Rodríguez-Benot
Pedro Aljama
Pedro Aljama
Rafael Solana
Rafael Solana
author_facet Juan Molina
Ana Navas
María-Luisa Agüera
María-Luisa Agüera
Cristian Rodelo-Haad
Corona Alonso
Corona Alonso
Alberto Rodríguez-Benot
Alberto Rodríguez-Benot
Pedro Aljama
Pedro Aljama
Rafael Solana
Rafael Solana
author_sort Juan Molina
collection DOAJ
description The consolidation of single antigen beads (SAB-panIgG) assay in the detection of preformed anti-human leukocyte antigen (HLA) antibodies has improved transplantation success. However, its high sensitivity has limited the allograft allocation for sensitized patients, increasing their waiting time. A modification of the standard SAB-panIgG assay allows the detection of that subset of antibodies capable of binding C1q (SAB-C1q assay). However, the clinical usefulness of SAB-C1q assay for determining the unacceptable mismatches is under discussion. We retrospectively analyzed the impact of preformed donor-specific anti-HLA antibodies (DSA) according to the C1q-binding ability on allograft outcome, examining 389 single-kidney transplanted patients from deceased donors. Recipients with preformed C1q-binding DSA showed the lowest allograft survival up to 7 years (40.7%) compared to patients with preformed non-C1q-binding DSA (73.4%; p = 0.001) and without DSA (79.1%; p < 0.001). Allograft survival rate was similar between patients with preformed non-C1q-binding DSA and patients without preformed DSA (p = 0.403). Interestingly, among the high-mean fluorescence intensity DSA (≥10,000) population (n = 46), those patients whose DSA were further capable of binding C1q showed a poorer allograft outcome (38.4 vs. 68.9%; p = 0.041). Moreover, in our multivariate predictive model for assessing the risk of allograft loss, the presence of C1q-binding DSA (HR 4.012; CI 95% 2.326–6.919; p < 0.001) but not of non-C1q-binding DSA (HR 1.389; CI 95% 0.784–2.461; p = 0.260) remained an independent predictor after stratifying the DSA population according to the C1q-binding ability and adjusting the model for other pre-transplantation predictive factors including donor age, cold-ischemia time, and HLA-DR mismatches. In conclusion, the unacceptable mismatch definition according to the SAB-C1q assay would improve the risk stratification of allograft loss and increase the limited allograft allocation of highly sensitized patients, shortening their waiting time.
first_indexed 2024-04-12T17:34:18Z
format Article
id doaj.art-e8fb1c78854942a9a41048fe2f497d45
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-12T17:34:18Z
publishDate 2017-10-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-e8fb1c78854942a9a41048fe2f497d452022-12-22T03:23:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01310272072Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft OutcomeJuan Molina0Ana Navas1María-Luisa Agüera2María-Luisa Agüera3Cristian Rodelo-Haad4Corona Alonso5Corona Alonso6Alberto Rodríguez-Benot7Alberto Rodríguez-Benot8Pedro Aljama9Pedro Aljama10Rafael Solana11Rafael Solana12Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainDepartment of Nephrology, Reina Sofia University Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainDepartment of Allergy and Immunology, Reina Sofia University Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainDepartment of Nephrology, Reina Sofia University Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainDepartment of Nephrology, Reina Sofia University Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, SpainDepartment of Immunology, Infanta Cristina University Hospital, Badajoz, SpainThe consolidation of single antigen beads (SAB-panIgG) assay in the detection of preformed anti-human leukocyte antigen (HLA) antibodies has improved transplantation success. However, its high sensitivity has limited the allograft allocation for sensitized patients, increasing their waiting time. A modification of the standard SAB-panIgG assay allows the detection of that subset of antibodies capable of binding C1q (SAB-C1q assay). However, the clinical usefulness of SAB-C1q assay for determining the unacceptable mismatches is under discussion. We retrospectively analyzed the impact of preformed donor-specific anti-HLA antibodies (DSA) according to the C1q-binding ability on allograft outcome, examining 389 single-kidney transplanted patients from deceased donors. Recipients with preformed C1q-binding DSA showed the lowest allograft survival up to 7 years (40.7%) compared to patients with preformed non-C1q-binding DSA (73.4%; p = 0.001) and without DSA (79.1%; p < 0.001). Allograft survival rate was similar between patients with preformed non-C1q-binding DSA and patients without preformed DSA (p = 0.403). Interestingly, among the high-mean fluorescence intensity DSA (≥10,000) population (n = 46), those patients whose DSA were further capable of binding C1q showed a poorer allograft outcome (38.4 vs. 68.9%; p = 0.041). Moreover, in our multivariate predictive model for assessing the risk of allograft loss, the presence of C1q-binding DSA (HR 4.012; CI 95% 2.326–6.919; p < 0.001) but not of non-C1q-binding DSA (HR 1.389; CI 95% 0.784–2.461; p = 0.260) remained an independent predictor after stratifying the DSA population according to the C1q-binding ability and adjusting the model for other pre-transplantation predictive factors including donor age, cold-ischemia time, and HLA-DR mismatches. In conclusion, the unacceptable mismatch definition according to the SAB-C1q assay would improve the risk stratification of allograft loss and increase the limited allograft allocation of highly sensitized patients, shortening their waiting time.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01310/fullallograft-loss riskC1q-binding antibodieskidney allograft survivalkidney transplantationpreformed anti-HLA antibodiessingle antigen beads assay
spellingShingle Juan Molina
Ana Navas
María-Luisa Agüera
María-Luisa Agüera
Cristian Rodelo-Haad
Corona Alonso
Corona Alonso
Alberto Rodríguez-Benot
Alberto Rodríguez-Benot
Pedro Aljama
Pedro Aljama
Rafael Solana
Rafael Solana
Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome
Frontiers in Immunology
allograft-loss risk
C1q-binding antibodies
kidney allograft survival
kidney transplantation
preformed anti-HLA antibodies
single antigen beads assay
title Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome
title_full Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome
title_fullStr Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome
title_full_unstemmed Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome
title_short Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome
title_sort impact of preformed donor specific anti human leukocyte antigen antibody c1q binding ability on kidney allograft outcome
topic allograft-loss risk
C1q-binding antibodies
kidney allograft survival
kidney transplantation
preformed anti-HLA antibodies
single antigen beads assay
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.01310/full
work_keys_str_mv AT juanmolina impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT ananavas impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT marialuisaaguera impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT marialuisaaguera impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT cristianrodelohaad impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT coronaalonso impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT coronaalonso impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT albertorodriguezbenot impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT albertorodriguezbenot impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT pedroaljama impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT pedroaljama impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT rafaelsolana impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome
AT rafaelsolana impactofpreformeddonorspecificantihumanleukocyteantigenantibodyc1qbindingabilityonkidneyallograftoutcome