Ann Lab Med.  2018 Sep;38(5):450-457. 10.3343/alm.2018.38.5.450.

Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients

Affiliations
  • 1Division of Nephrology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea.
  • 2Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. ejoh@catholic.ac.kr
  • 3Department of Laboratory Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea.
  • 4Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. chungbh@catholic.ac.kr
  • 5Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract

BACKGROUND
Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients.
METHODS
Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics.
RESULTS
Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti-AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (−) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017-24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti-AT1R.
CONCLUSIONS
Pre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue.

Keyword

Angiotensin II type 1 receptor; Donor-specific anti-HLA antibody; Microvascular inflammation; Kidney transplantation

MeSH Terms

Allografts
Angiotensin II*
Angiotensins*
Antibodies*
Humans
Inflammation
Kidney Transplantation
Kidney*
Major Histocompatibility Complex*
Receptor, Angiotensin, Type 1
Retrospective Studies
Risk Factors
Angiotensin II
Angiotensins
Antibodies
Receptor, Angiotensin, Type 1

Figure

  • Fig. 1 Synergistic impacts of HLA-DSA and anti-AT1R on MVI. Detection of MVI was the highest in patients with both HLA-DSA and anti-AT1R, showing a synergistic impact (P<0.001, chi-square for trend). In patients without HLA-DSA, the presence of anti-AT1R was significantly associated with the development of MVI (12/116 vs 22/111, P=0.046). HLA-DSA increased the incidence of MVI in both patients with (P=0.001) and without (P=0.001) anti-AT1Rs.Abbreviations: DSA, donor-specific antibody; anti-AT1R, angiotensin II type 1 receptor antibody.

  • Fig. 2 Comparison of allograft survival. (A) Patients that were HLA-DSA (+) showed significantly lower allograft survival rates (P=0.037), and (B) patients that were anti-AT1R (+) showed significantly lower allograft survival rates (P=0.042). (C) There was no effect of the presence of anti-MICA on allograft survival. (D) The HLA-DSA(−)AT1R(+) group showed a tendency for poorer survival compared with the HLA-DSA(+)AT1R(−) group. Survival was poorest in the HLA-DSA(+)AT1R(+) group (P=0.069).Abbreviations: DSA, donor-specific antibody; anti-AT1R, angiotensin II type 1 receptor antibody; anti-MICA, MHC class I-related chain A antibody.


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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, Hee Jae Huh, Kyo Won Lee, Jae Berm Park, Sung-Joo Kim, Wooseong Huh, Hye Ryoun Jang, Ghee Young Kwon, Hyung Hwan Moon, Eun-Suk Kang
Ann Lab Med. 2020;40(5):398-408.    doi: 10.3343/alm.2020.40.5.398.

Causes of Positive Pretransplant Crossmatches in the Absence of Donor-Specific Anti-Human Leukocyte Antigen Antibodies: A Single-Center Experience
Hyunhye Kang, Jaeeun Yoo, Sang-Yoon Lee, Eun-Jee Oh
Ann Lab Med. 2021;41(4):429-435.    doi: 10.3343/alm.2021.41.4.429.

Angiotensin II type 1 receptor antibodies in kidney transplantation
Hyeyoung Lee, Eun-Jee Oh
J Korean Soc Transplant. 2019;33(1):6-12.    doi: 10.4285/jkstn.2019.33.1.6.


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