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Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients

Antibody-mediated rejection is a common cause of early kidney allograft loss but the specifics of antibody measurement, therapies and endpoints have not been universally defined. In this retrospective study, we assessed the performance of risk stratification using systematic donor-specific antibody...

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Autores principales: Sigurjonsdottir, Vaka K., Purington, Natasha, Chaudhuri, Abanti, Zhang, Bing M., Fernandez-Vina, Marcelo, Palsson, Runolfur, Kambham, Neeraja, Charu, Vivek, Piburn, Kim, Maestretti, Lynn, Shah, Anika, Gallo, Amy, Concepcion, Waldo, Grimm, Paul C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386741/
https://www.ncbi.nlm.nih.gov/pubmed/35992747
http://dx.doi.org/10.3389/ti.2021.10158
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author Sigurjonsdottir, Vaka K.
Purington, Natasha
Chaudhuri, Abanti
Zhang, Bing M.
Fernandez-Vina, Marcelo
Palsson, Runolfur
Kambham, Neeraja
Charu, Vivek
Piburn, Kim
Maestretti, Lynn
Shah, Anika
Gallo, Amy
Concepcion, Waldo
Grimm, Paul C.
author_facet Sigurjonsdottir, Vaka K.
Purington, Natasha
Chaudhuri, Abanti
Zhang, Bing M.
Fernandez-Vina, Marcelo
Palsson, Runolfur
Kambham, Neeraja
Charu, Vivek
Piburn, Kim
Maestretti, Lynn
Shah, Anika
Gallo, Amy
Concepcion, Waldo
Grimm, Paul C.
author_sort Sigurjonsdottir, Vaka K.
collection PubMed
description Antibody-mediated rejection is a common cause of early kidney allograft loss but the specifics of antibody measurement, therapies and endpoints have not been universally defined. In this retrospective study, we assessed the performance of risk stratification using systematic donor-specific antibody (DSA) monitoring. Included in the study were children who underwent kidney transplantation between January 1, 2010 and March 1, 2018 at Stanford, with at least 12-months follow-up. A total of 233 patients were included with a mean follow-up time of 45 (range, 9–108) months. Median age at transplant was 12.3 years, 46.8% were female, and 76% had a deceased donor transplant. Fifty-two (22%) formed C1q-binding de novo donor-specific antibodies (C1q-dnDSA). After a standardized augmented immunosuppressive protocol was implemented, C1q-dnDSA disappeared in 31 (58.5%). Graft failure occurred in 16 patients at a median of 54 (range, 5–83) months, of whom 14 formed dnDSA. The 14 patients who lost their graft due to rejection, all had persistent C1q-dnDSA. C1q-binding status improved the individual risk assessment, with persistent; C1q binding yielding the strongest independent association of graft failure (hazard ratio, 45.5; 95% confidence interval, 11.7–177.4). C1q-dnDSA is more useful than standard dnDSA as a noninvasive biomarker for identifying patients at the highest risk of graft failure.
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spelling pubmed-93867412022-08-19 Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients Sigurjonsdottir, Vaka K. Purington, Natasha Chaudhuri, Abanti Zhang, Bing M. Fernandez-Vina, Marcelo Palsson, Runolfur Kambham, Neeraja Charu, Vivek Piburn, Kim Maestretti, Lynn Shah, Anika Gallo, Amy Concepcion, Waldo Grimm, Paul C. Transpl Int Health Archive Antibody-mediated rejection is a common cause of early kidney allograft loss but the specifics of antibody measurement, therapies and endpoints have not been universally defined. In this retrospective study, we assessed the performance of risk stratification using systematic donor-specific antibody (DSA) monitoring. Included in the study were children who underwent kidney transplantation between January 1, 2010 and March 1, 2018 at Stanford, with at least 12-months follow-up. A total of 233 patients were included with a mean follow-up time of 45 (range, 9–108) months. Median age at transplant was 12.3 years, 46.8% were female, and 76% had a deceased donor transplant. Fifty-two (22%) formed C1q-binding de novo donor-specific antibodies (C1q-dnDSA). After a standardized augmented immunosuppressive protocol was implemented, C1q-dnDSA disappeared in 31 (58.5%). Graft failure occurred in 16 patients at a median of 54 (range, 5–83) months, of whom 14 formed dnDSA. The 14 patients who lost their graft due to rejection, all had persistent C1q-dnDSA. C1q-binding status improved the individual risk assessment, with persistent; C1q binding yielding the strongest independent association of graft failure (hazard ratio, 45.5; 95% confidence interval, 11.7–177.4). C1q-dnDSA is more useful than standard dnDSA as a noninvasive biomarker for identifying patients at the highest risk of graft failure. Frontiers Media S.A. 2022-03-16 /pmc/articles/PMC9386741/ /pubmed/35992747 http://dx.doi.org/10.3389/ti.2021.10158 Text en Copyright © 2022 Sigurjonsdottir, Purington, Chaudhuri, Zhang, Fernandez-Vina, Palsson, Kambham, Charu, Piburn, Maestretti, Shah, Gallo, Concepcion and Grimm. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Health Archive
Sigurjonsdottir, Vaka K.
Purington, Natasha
Chaudhuri, Abanti
Zhang, Bing M.
Fernandez-Vina, Marcelo
Palsson, Runolfur
Kambham, Neeraja
Charu, Vivek
Piburn, Kim
Maestretti, Lynn
Shah, Anika
Gallo, Amy
Concepcion, Waldo
Grimm, Paul C.
Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients
title Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients
title_full Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients
title_fullStr Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients
title_full_unstemmed Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients
title_short Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients
title_sort complement-binding donor-specific anti-hla antibodies: biomarker for immunologic risk stratification in pediatric kidney transplantation recipients
topic Health Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386741/
https://www.ncbi.nlm.nih.gov/pubmed/35992747
http://dx.doi.org/10.3389/ti.2021.10158
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