Abstract: PO2052
Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients with Kidney Allograft Antibody-Mediated Rejection
Session Information
- Transplantation: Evaluating Kidney Graft Injury - Pathways and Biomarkers
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1901 Transplantation: Basic
Authors
- Clotet Freixas, Sergi, University Health Network, Toronto, Ontario, Canada
- Kotlyar, Max, University Health Network, Toronto, Ontario, Canada
- McEvoy, Caitriona M., University Health Network, Toronto, Ontario, Canada
- Pastrello, Chiara, University Health Network, Toronto, Ontario, Canada
- Rodriguez Ramirez, Sonia, University Health Network, Toronto, Ontario, Canada
- Farkona, Sofia, University Health Network, Toronto, Ontario, Canada
- Cardinal, Heloise, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Quebec, Canada
- Dieudé, Mélanie, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Quebec, Canada
- Hebert, Marie-Josee, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Quebec, Canada
- Li, Yanhong, University Health Network, Toronto, Ontario, Canada
- John, Rohan, University Health Network, Toronto, Ontario, Canada
- Chruscinski, Andrzej, University Health Network, Toronto, Ontario, Canada
- Konvalinka, Ana, University Health Network, Toronto, Ontario, Canada
Background
Antibody-mediated rejection (AMR) causes >50% of late kidney graft losses. In addition to anti-HLA donor-specific antibodies (DSA), 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 (ATN). IgM and IgG antibodies against 134 non-HLA antigens were measured in serum samples collected pre-transplant or at the time of diagnosis.
Results
Fifteen non-HLA antibodies were significantly increased (p<0.05) in AMR and mixed rejection compared to ACR or ATN pre-transplant, and seven at diagnosis. AMR and mixed cases showed significantly increased pre-transplant levels of IgG anti-Ro/SS-A and anti-CENP-B, compared to 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 DSA (p<0.05). Significant increases in IgG anti-Ro/SS-A and IgM anti-CENP-B antibodies in AMR/mixed rejection compared to ACR were reproduced in an external cohort of 60 kidney transplant patients.
Conclusion
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.