Ann Lab Med 2020; 40(5): 398-408  https://doi.org/10.3343/alm.2020.40.5.398
Pre-Transplant Angiotensin II Type 1 Receptor Antibodies and Anti-Endothelial Cell Antibodies Predict Graft Function and Allograft Rejection in a Low-Risk Kidney Transplantation Setting
Shinae Yu, M.D.1, Hee Jae Huh, M.D.2, Kyo Won Lee, M.D.3,4, Jae Berm Park, M.D.3,4, Sung-Joo Kim, M.D.3,4, Wooseong Huh, M.D.4,5, Hye Ryoun Jang, M.D.4,5, Ghee Young Kwon, M.D.6, Hyung Hwan Moon, M.D.7, and Eun-Suk Kang, M.D.2,4
1Department of Laboratory Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea; Departments of 2Laboratory Medicine and Genetics, 3Surgery, 4Organ Transplantation Center, 5Internal Medicine, 6Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 7Department of Surgery Kosin University Gospel Hospital, Medical College of Kosin University, Busan, Korea
Corresponding author: Eun-Suk Kang, M.D., Ph.D.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel.: +82-2-3410-2703
Fax: +82-2-3410-2719
E-mail: eskang@skku.edu
Received: November 13, 2019; Revised: February 17, 2020; Accepted: March 3, 2020; Published online: September 1, 2020.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients.
Methods: In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes.
Results: Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant.
Conclusions: Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.
Keywords: Non-HLA antibodies, Anti- angiotensin II type 1 receptor antibodies, Anti-endothelial cell antibodies, Endothelial cell crossmatch, Kidney transplantation, Outcome, Low-risk



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