Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation
Year: 2020
Type: article
Study design: Observational Study
Abstract: Introduction Autoantibody to angiotensin II type 1 receptor (AT1R-Ab) has been recognized as a non-human leukocyte antigen (HLA) antibody relevant in transplantation. Endothelin type A receptor antibody (ETAR-Ab) has been strongly associated with AT1R-Ab, but the data in kidney transplantation are scarce. Methods We examined the relationship of ETAR-Ab and AT1R-Ab with clinical outcomes, biopsy findings, inflammatory cytokines, and HLA donor-specific antibody (DSA) in a cohort of pediatric renal transplant recipients. Sixty-five patients were longitudinally monitored for ETAR-Ab, AT1R-Ab, HLA DSA, interleukin (IL)-8, tumor necrosis factor-α, IL-1β, interferon-γ, IL-17, IL-6, renal dysfunction, hypertension, rejection, and allograft loss during the first 2 years post-transplant. Results Fifteen patients (23%) had AT1R-Ab alone, 1 (2%) had ETAR-Ab alone, 23 (35%) had both ETAR-Ab and AT1R-Ab, and 26 (40%) were negative for both antibodies at all timepoints. Having both ETAR-Ab and AT1R-Ab was associated with >30% decline in estimated glomerular filtration rate ( P = 0.024), arteritis ( P = 0.016), and elevated IL-8 levels ( P = 0.010), but not rejection, HLA DSA, or allograft loss. Having both antibodies resulted in greater increases in IL-8 compared with AT1R-Ab alone, even when controlled for additional clinical factors, including HLA DSA ( P = 0.012). Conclusion Our study demonstrates that, in pediatric kidney transplantation, ETAR-Ab is highly associated with AT1R-Ab, but there are a subset of patients with AT1R-Ab alone. Having both antibodies is significantly associated with arteritis, elevated IL-8, and decline in renal function, and our results suggest possible interaction effects. Better understanding of this interaction may be informative in developing protocols for testing, treatment, and prevention of allograft injury.
Source: Kidney International Reports
Institutions: University of California, Los Angeles, Duke University
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,625
Funders: National Kidney Foundation, American Society of Nephrology, Duke University, Israel National Road Safety Authority, National Institutes of Health, University of California, Los Angeles, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G2797253369, G3756175955, Translational Research Training in Pediatric Nephrology, Mapping Immune Responses to CMV in Renal Transplant Recipients, Systems Immunolobiology of Antibiotic-Persistent MRSA Infection, G9000252277, Innate-Adaptive Immunoregulation in Liver Transplant Ischemia/Reperfusion Injury, The role of HLA and its coreceptors in endothelial cell activation and leukocyte recruitment in antibody-mediated transplant rejection, UCLA Clinical and Translational Science Institute, Understanding the Interface of Allo and Auto-Immunity: The Impact of Angiotensin II Type 1 Receptor Antibodies in Pediatric Kidney Transplant Recipients
OpenAlex ID: W3083324517