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Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection
Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR. METHO...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454907/ https://www.ncbi.nlm.nih.gov/pubmed/34557585 http://dx.doi.org/10.1097/TXD.0000000000001215 |
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author | Clotet-Freixas, Sergi Kotlyar, Max McEvoy, Caitriona M. Pastrello, Chiara Rodríguez-Ramírez, Sonia Farkona, Sofia Cardinal, Heloise Dieudé, Mélanie Hébert, Marie-Josée Li, Yanhong Famure, Olusegun Chen, Peixuen Kim, S. Joseph Chan, Emilie Jurisica, Igor John, Rohan Chruscinski, Andrzej Konvalinka, Ana |
author_facet | Clotet-Freixas, Sergi Kotlyar, Max McEvoy, Caitriona M. Pastrello, Chiara Rodríguez-Ramírez, Sonia Farkona, Sofia Cardinal, Heloise Dieudé, Mélanie Hébert, Marie-Josée Li, Yanhong Famure, Olusegun Chen, Peixuen Kim, S. Joseph Chan, Emilie Jurisica, Igor John, Rohan Chruscinski, Andrzej Konvalinka, Ana |
author_sort | Clotet-Freixas, Sergi |
collection | PubMed |
description | Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR. METHODS. We analyzed non-HLA antibodies in sera from 80 kidney transplant patients with AMR, mixed rejection, acute cellular rejection (ACR), or acute tubular necrosis. IgM and IgG antibodies against 134 non-HLA antigens were measured in serum samples collected pretransplant or at the time of diagnosis. RESULTS. Fifteen non-HLA antibodies were significantly increased (P < 0.05) in AMR and mixed rejection compared with ACR or acute tubular necrosis pretransplant, and 7 at diagnosis. AMR and mixed cases showed significantly increased pretransplant levels of IgG anti-Ro/Sjögren syndrome-antigen A (SS-A) and anti-major centromere autoantigen (CENP)-B, compared with ACR. Together with IgM anti-CENP-B and anti-La/SS-B, these antibodies were significantly increased in AMR/mixed rejection at diagnosis. Increased IgG anti-Ro/SS-A, IgG anti-CENP-B, and IgM anti-La/SS-B were associated with the presence of microvascular lesions and class-II donor-specific antibodies (P < 0.05). Significant increases in IgG anti-Ro/SS-A and IgM anti-CENP-B antibodies in AMR/mixed rejection compared with ACR were reproduced in an external cohort of 60 kidney transplant patients. CONCLUSIONS. This is the first study implicating autoantibodies anti-Ro/SS-A and anti-CENP-B in AMR. These antibodies may participate in the crosstalk between autoimmunity and alloimmunity in kidney AMR. |
format | Online Article Text |
id | pubmed-8454907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-84549072021-09-22 Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection Clotet-Freixas, Sergi Kotlyar, Max McEvoy, Caitriona M. Pastrello, Chiara Rodríguez-Ramírez, Sonia Farkona, Sofia Cardinal, Heloise Dieudé, Mélanie Hébert, Marie-Josée Li, Yanhong Famure, Olusegun Chen, Peixuen Kim, S. Joseph Chan, Emilie Jurisica, Igor John, Rohan Chruscinski, Andrzej Konvalinka, Ana Transplant Direct Kidney Transplantation Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR. METHODS. We analyzed non-HLA antibodies in sera from 80 kidney transplant patients with AMR, mixed rejection, acute cellular rejection (ACR), or acute tubular necrosis. IgM and IgG antibodies against 134 non-HLA antigens were measured in serum samples collected pretransplant or at the time of diagnosis. RESULTS. Fifteen non-HLA antibodies were significantly increased (P < 0.05) in AMR and mixed rejection compared with ACR or acute tubular necrosis pretransplant, and 7 at diagnosis. AMR and mixed cases showed significantly increased pretransplant levels of IgG anti-Ro/Sjögren syndrome-antigen A (SS-A) and anti-major centromere autoantigen (CENP)-B, compared with ACR. Together with IgM anti-CENP-B and anti-La/SS-B, these antibodies were significantly increased in AMR/mixed rejection at diagnosis. Increased IgG anti-Ro/SS-A, IgG anti-CENP-B, and IgM anti-La/SS-B were associated with the presence of microvascular lesions and class-II donor-specific antibodies (P < 0.05). Significant increases in IgG anti-Ro/SS-A and IgM anti-CENP-B antibodies in AMR/mixed rejection compared with ACR were reproduced in an external cohort of 60 kidney transplant patients. CONCLUSIONS. This is the first study implicating autoantibodies anti-Ro/SS-A and anti-CENP-B in AMR. These antibodies may participate in the crosstalk between autoimmunity and alloimmunity in kidney AMR. Lippincott Williams & Wilkins 2021-09-20 /pmc/articles/PMC8454907/ /pubmed/34557585 http://dx.doi.org/10.1097/TXD.0000000000001215 Text en Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Kidney Transplantation Clotet-Freixas, Sergi Kotlyar, Max McEvoy, Caitriona M. Pastrello, Chiara Rodríguez-Ramírez, Sonia Farkona, Sofia Cardinal, Heloise Dieudé, Mélanie Hébert, Marie-Josée Li, Yanhong Famure, Olusegun Chen, Peixuen Kim, S. Joseph Chan, Emilie Jurisica, Igor John, Rohan Chruscinski, Andrzej Konvalinka, Ana Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection |
title | Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection |
title_full | Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection |
title_fullStr | Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection |
title_full_unstemmed | Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection |
title_short | Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection |
title_sort | increased autoantibodies against ro/ss-a, cenp-b, and la/ss-b in patients with kidney allograft antibody-mediated rejection |
topic | Kidney Transplantation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454907/ https://www.ncbi.nlm.nih.gov/pubmed/34557585 http://dx.doi.org/10.1097/TXD.0000000000001215 |
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