Characterization of Non HLA Antibodies in Kidney Transplant Recipients
1Kidney Transplant, Toronto General Hospital Research Institute, Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada, 2Kidney Transplant, Krembil Research Institute, University Health Network, Toronto, ON, Canada, 3Kidney Transplant, Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON, Canada
Meeting: 2020 American Transplant Congress
Abstract number: D-338
Keywords: Antibodies, B cells, Peptides, Rejection
Session Information
Date: Saturday, May 30, 2020
Session Name: Poster Session D: B-cell / Antibody /Autoimmunity
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Antibody mediated rejection (AMR) causes more than 60 percent of late graft failures in kidney transplants (KT). Although antiHLA donor specific antibodies are the main perpetrators of AMR, antibodies against non-HLA autoantigens are also associated with rejection and decreased long term graft survival
*Methods: Sera from patients who underwent a KT were obtained from the HLA laboratory. We utilized antigen microarray platform to screen for non HLA antibodies. Wilcox test was used to calculate p values
*Results: To define the repertoire of circulating nonHLA antibodies in a setting of graft injury, we performed an antigen microarray analysis of serum from 96 patients with kidney transplant. We compared cases with pure AMR (47) to those with acute cellular rejection (ACR) (16), mixed rejection (18) and acute tubular necrosis (ATN) (15). We measured antiHLA and nonHLA antibodies at the time of the biopsy. The microarray panels included 135 non-HLA antigens. Antibodies against 101 nonHLA antigens had MFI more than 200 and were analyzed further. Four nonHLA antibodies (against CENPB, TRIM21, TPM and HSPG2) were significantly different (p less than 0.05) between our comparator groups at the time of the biopsy. IgG antibodies against CENPB and TRIM21 proteins were significantly elevated in patients with pure AMR or mixed rejection, in comparison to patients with ACR or ATN (p less than 0.05). Anti-TPM IgG antibodies were significantly lower in pure AMR compared to mixed rejection. Only patients with pure AMR showed elevated levels of IgM antibody against HSPG2 antigen. In a subset of 30 patients, we conducted unbiased proteomic analyses of the glomerular and tubulointerstitial compartments. We found that HSPG2 was significantly decreased in the glomeruli of AMR vs ACR or ATN groups
*Conclusions: IgG antibodies against CENPB and TRIM21 proteins may potentially segregate patients with AMR from those with other pathologies. IgM antibodies against HSPG2 were increased in AMR patients with a concomitant decrease in glomerular HSPG2 protein, suggesting that these antibodies may play a role in glomerular basement membrane injury
To cite this abstract in AMA style:
Ramirez SRodriguez, Clotet-Freixas S, Mcevoy C, Kotlyar M, Jurisica I, Chruscinski A, Konvalinka A. Characterization of Non HLA Antibodies in Kidney Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/characterization-of-non-hla-antibodies-in-kidney-transplant-recipients/. Accessed March 6, 2021.« Back to 2020 American Transplant Congress