Association of positive pre-transplant angiotensin II type 1 receptor antibodies with clinical outcomes in lung transplant recipients |
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| Institution: | 1. Department of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Busan, 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;3. Department of Laboratory Medicine, Pusan National University, School of Medicine, Busan, Republic of Korea;4. Department of Internal Medicine, Pusan National University School of Medicine, Busan, Republic of Korea;5. 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;6. Division of Rheumatology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;7. Department of Thoracic and Cardiovascular Surgery, Busan Medical Center, Busan, Republic of Korea;1. Biology Department, Science and Arts University, Yazd, Iran;2. Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;3. Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;4. Department of Biological Sciences, Faculty of Engineering and Science, Science and Arts University, Yazd, Iran;1. Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Detroit, Michigan;2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan;3. Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile;4. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan;5. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan;6. Department of Computer Science, Wayne State University College of Engineering, Detroit, Michigan;7. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan;8. Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, Michigan |
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| Abstract: | IntroductionAutoantibodies 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.MethodsSeventy-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.ResultsSeventeen (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).ConclusionHigh 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. |
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