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...
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Frontiers Media S.A.
2017-10-01
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Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01310/full |
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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. |
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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 |
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