Association of positive pre-transplant angiotensin II type 1 receptor antibodies with clinical outcomes in lung transplant recipients

Bong Soo Son; Hyun Ji Lee; Woo Hyun Cho; Min Wook So; Jong Myung Park; Hye Ju Yeo

doi:10.1016/j.trim.2023.101901

Association of positive pre-transplant angiotensin II type 1 receptor antibodies with clinical outcomes in lung transplant recipients

Transpl Immunol. 2023 Oct:80:101901. doi: 10.1016/j.trim.2023.101901. Epub 2023 Jul 11.

Authors

Bong Soo Son¹, Hyun Ji Lee², Woo Hyun Cho³, Min Wook So⁴, Jong Myung Park⁵, Hye Ju Yeo⁶

Affiliations

¹ Department of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Busan, Republic of Korea; Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
² Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; Department of Laboratory Medicine, Pusan National University, School of Medicine, Busan, Republic of Korea.
³ Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; Department of Internal Medicine, Pusan National University School of Medicine, Busan, Republic of Korea; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
⁴ Division of Rheumatology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea.
⁵ Department of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Busan, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Busan Medical Center, Busan, Republic of Korea.
⁶ Transplantation Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; Department of Internal Medicine, Pusan National University School of Medicine, Busan, Republic of Korea; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea. Electronic address: dugpwn@naver.com.

PMID: 37442212
DOI: 10.1016/j.trim.2023.101901

Abstract

Introduction: Autoantibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been previously associated with de novo donor-specific antibody (DSA) formation in lung transplantation. However, data regarding the clinical significance of AT1R-Ab in long-term graft function after lung transplantation are lacking.

Methods: Seventy-one patients who underwent lung transplantation between July 2016 and January 2020 were enrolled in this study. We examined the relationship between pre-transplant AT1R-Ab levels and graft function, clinical outcomes, and human leukocyte antigen (HLA) DSA levels during the first 3 years post-transplantation.

Results: Seventeen (23.9%) patients were AT1R-Ab-positive, and 54 (76.1%) were AT1R-Ab-negative. The median antibody value of the AT1R-Ab-positive group was 18 [18-22.5] U/mL, while that of the AT1R-Ab-negative group was 5.1 [3.5-8.0] U/mL (p < 0.001). There was no significant difference in the median acute cellular rejection (ACR) scores between the two groups (median [interquartile range] 1 [0.8-3] vs. 0.7 [0-1]; p = 0.145). However, there was a significant difference in the distribution of the ACR scores between the two groups (p = 0.015). Most (41.2%) patients in the pre-transplant AT1R-positive group scored above 1. The incidence of de novo DSA was also higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (52.9% vs. 20.4%, p = 0.009). The incidence of chronic lung allograft dysfunction (CLAD) within 3 years was significantly higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (58.3% vs. 11.8%; p < 0.001). In the multivariate Cox regression analysis, AT1R-Ab positivity (hazard ratio, 9.46; 95% confidence interval, 2.89-30.94; p < 0.001) was significantly associated with early CLAD. Furthermore, Kaplan-Meier analysis showed that AT1R-Ab-positive patients had a shorter survival time (χ² = 39.62, p < 0.001).

Conclusion: High AT1R-Ab levels in the pre-transplant serum of lung recipients were associated with the development of de novo HLA-DSA, ACR, early CLAD, and short survival.

Keywords: Angiotensin II type 1 receptor; Lung transplantation; Mortality; Rejection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies
Graft Rejection
Graft Survival
HLA Antigens
Humans
Lung
Receptor, Angiotensin, Type 1*
Retrospective Studies
Transplant Recipients*
Transplantation, Homologous

Substances

Receptor, Angiotensin, Type 1
Autoantibodies
HLA Antigens