Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection
Background. 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 o...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2021-10-01
|
| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001215 |
| _version_ | 1818620368910286848 |
|---|---|
| author | Sergi Clotet-Freixas, PhD Max Kotlyar, PhD Caitriona M. McEvoy, MD, PhD Chiara Pastrello, PhD Sonia Rodríguez-Ramírez, MD Sofia Farkona, PhD Heloise Cardinal, MD, PhD Mélanie Dieudé, PhD Marie-Josée Hébert, MD, PhD Yanhong Li, BSc Olusegun Famure, MPH, MEd, Peixuen Chen, HBSc, BScN S. Joseph Kim, MD, PhD Emilie Chan, MD Igor Jurisica, PhD Rohan John, MD Andrzej Chruscinski, MD, PhD Ana Konvalinka, MD, PhD |
| author_facet | Sergi Clotet-Freixas, PhD Max Kotlyar, PhD Caitriona M. McEvoy, MD, PhD Chiara Pastrello, PhD Sonia Rodríguez-Ramírez, MD Sofia Farkona, PhD Heloise Cardinal, MD, PhD Mélanie Dieudé, PhD Marie-Josée Hébert, MD, PhD Yanhong Li, BSc Olusegun Famure, MPH, MEd, Peixuen Chen, HBSc, BScN S. Joseph Kim, MD, PhD Emilie Chan, MD Igor Jurisica, PhD Rohan John, MD Andrzej Chruscinski, MD, PhD Ana Konvalinka, MD, PhD |
| author_sort | Sergi Clotet-Freixas, PhD |
| collection | DOAJ |
| description | Background. 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. |
| first_indexed | 2024-12-16T17:52:17Z |
| format | Article |
| id | doaj.art-ad1e0b13d49a4debb40ec96a023a64d7 |
| institution | Directory Open Access Journal |
| issn | 2373-8731 |
| language | English |
| last_indexed | 2024-12-16T17:52:17Z |
| publishDate | 2021-10-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj.art-ad1e0b13d49a4debb40ec96a023a64d72022-12-21T22:22:16ZengWolters KluwerTransplantation Direct2373-87312021-10-01710e76810.1097/TXD.0000000000001215202110000-00023Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated RejectionSergi Clotet-Freixas, PhD0Max Kotlyar, PhD1Caitriona M. McEvoy, MD, PhD2Chiara Pastrello, PhD3Sonia Rodríguez-Ramírez, MD4Sofia Farkona, PhD5Heloise Cardinal, MD, PhD6Mélanie Dieudé, PhD7Marie-Josée Hébert, MD, PhD8Yanhong Li, BSc9Olusegun Famure, MPH, MEd,10Peixuen Chen, HBSc, BScN11S. Joseph Kim, MD, PhD12Emilie Chan, MD13Igor Jurisica, PhD14Rohan John, MD15Andrzej Chruscinski, MD, PhD16Ana Konvalinka, MD, PhD171 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.3 Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.3 Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.5 Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Canada.5 Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Canada.5 Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.8 Department of Medicine, Division of Nephrology, University Health Network, Toronto, Canada.3 Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.Background. 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.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001215 |
| spellingShingle | Sergi Clotet-Freixas, PhD Max Kotlyar, PhD Caitriona M. McEvoy, MD, PhD Chiara Pastrello, PhD Sonia Rodríguez-Ramírez, MD Sofia Farkona, PhD Heloise Cardinal, MD, PhD Mélanie Dieudé, PhD Marie-Josée Hébert, MD, PhD Yanhong Li, BSc Olusegun Famure, MPH, MEd, Peixuen Chen, HBSc, BScN S. Joseph Kim, MD, PhD Emilie Chan, MD Igor Jurisica, PhD Rohan John, MD Andrzej Chruscinski, MD, PhD Ana Konvalinka, MD, PhD Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection Transplantation Direct |
| 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 |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001215 |
| work_keys_str_mv | AT sergiclotetfreixasphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT maxkotlyarphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT caitrionammcevoymdphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT chiarapastrellophd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT soniarodriguezramirezmd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT sofiafarkonaphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT heloisecardinalmdphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT melaniedieudephd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT mariejoseehebertmdphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT yanhonglibsc increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT olusegunfamuremphmed increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT peixuenchenhbscbscn increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT sjosephkimmdphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT emiliechanmd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT igorjurisicaphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT rohanjohnmd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT andrzejchruscinskimdphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection AT anakonvalinkamdphd increasedautoantibodiesagainstrossacenpbandlassbinpatientswithkidneyallograftantibodymediatedrejection |