Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection

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

doi:10.1097/TXD.0000000000001215

Transplantation Direct (Oct 2021)

Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection

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

Affiliations

Sergi Clotet-Freixas, PhD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Max Kotlyar, PhD: 3 Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute University Health Network, Toronto, Canada.
Caitriona M. McEvoy, MD, PhD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Chiara Pastrello, PhD: 3 Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute University Health Network, Toronto, Canada.
Sonia Rodríguez-Ramírez, MD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Sofia Farkona, PhD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Heloise Cardinal, MD, PhD: 5 Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Canada.
Mélanie Dieudé, PhD: 5 Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Canada.
Marie-Josée Hébert, MD, PhD: 5 Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Canada.
Yanhong Li, BSc: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Olusegun Famure, MPH, MEd,: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Peixuen Chen, HBSc, BScN: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
S. Joseph Kim, MD, PhD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Emilie Chan, MD: 8 Department of Medicine, Division of Nephrology, University Health Network, Toronto, Canada.
Igor Jurisica, PhD: 3 Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute University Health Network, Toronto, Canada.
Rohan John, MD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Andrzej Chruscinski, MD, PhD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Ana Konvalinka, MD, PhD: 1 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.

DOI: https://doi.org/10.1097/TXD.0000000000001215
Journal volume & issue: Vol. 7, no. 10
p. e768

Abstract

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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.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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