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Assessing the potential of angiotensin II type 1 receptor and donor specific anti-endothelial cell antibodies to predict long-term kidney graft outcome
Authors:David F. Pinelli  John J. Friedewald  Kelley M.K. Haarberg  Shree L. Radhakrishnan  Jennifer R. Zitzner  Wendy E. Hanshew  Anat R. Tambur
Affiliation:1. Northwestern University Feinberg School of Medicine, Comprehensive Transplant Center, Division of Transplant Surgery, 303 E Chicago Ave, Tarry Building Suite 11-763, Chicago, IL 60611, USA;2. Northwestern University, Division of Nephrology and Hypertension, Department of Medicine, 251 East Huron Street, Galter Suite 3-150, Chicago, IL 60611, USA
Abstract:
Endothelial cell antigens have been reported as potential targets for antibodies in the context of organ transplantation, leading to increased risk for graft failure. Serum samples from 142 consecutive living donor kidney recipients were tested for the presence of antibodies to angiotensin II – type 1 receptor (AT1R), donor endothelial cells, and donor HLA. Graft survival was monitored for five years post-transplant, and secondary outcomes, including biopsy-proven rejection, proteinuria, biopsy-proven vasculopathy, and renal function based on serum creatinine were also assessed for the first two to three years. AT1R antibody levels were positive (>17 U/mL) in 11.3%, 18.8% and 8.1% of patients pre-transplant, post-transplant and at time of indication biopsy, respectively. XM-ONE assay was positive in 17.6% of patients pre-transplant (7 IgG+; 15 IgM+; 3 IgG+/IgM+). Overall, 4 patients experienced antibody-mediated rejection (AMR), 31 borderline cellular rejection (BCR), 19 cellular rejection (CR) and 3 mixed AMR and CR within the first 24 months. While pre-existing and de novo donor-specific HLA antibodies were associated with graft failure and many secondary outcomes, no statistical association was found for either anti-endothelial or anti-AT1R antibodies, indicating that these tests may not be the best predictors of graft outcome in living donor renal transplantation.
Keywords:AT1R  angiotensin II type-1 receptor  HLA  human leukocyte antigen  AMR  antibody-mediated rejection  CR  cellular rejection  BCR  borderline cellular rejection  AECAs  anti-endothelial cell antibodies  SOC  standard of care  DSA  donor-specific antibody  ELISA  enzyme-linked immunosorbent assay  FSGS  focal segmental glomerulosclerosis  MICA/MICB  major histocompatibility complex class I chain related antigen A and B  UA  urinalysis  Transplant  Endothelial cells  Antibodies  HLA
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