Antibodies to angiotensin II type 1 receptor and endothelin type A receptor are associated with cytokine production enriched for type 2 immune response and antibody production in pediatric kidney transplant recipients
Year: 2025
Type: article
Study design: Observational Study
Abstract: Activating antibodies to angiotensin II type 1 receptor (AT1R) and endothelin type A receptor (ETAR) have been associated with rejection, allograft loss, decline in allograft function, and development of human leukocyte antigen donor-specific antibodies in kidney transplantation. Understanding immune dysregulation and inflammatory signatures associated with these antibodies is important for generating targeted investigations of pathogenesis. We investigated a panel of 38 cytokines in a multicenter cohort of 133 pediatric kidney transplant recipients with 1 to 2 years of follow up to further elucidate AT1R and ETAR-Ab-associated inflammatory signatures. Pretransplant and posttransplant blood samples (n = 483) were tested for AT1R-Ab, ETAR-Ab, and 38 cytokines. The relationship between AT1R and/or ETAR-Ab positivity and cytokine elevations were evaluated accounting for demographic and clinical factors. AT1R and/or ETAR-Ab positivity was associated with elevations in 33 of the 38 cytokines, with some elevations resolving or intensifying on posttransplant vs pretransplant samples. Interrogation of these data using z-score comparisons and principal component analyses revealed a strong signal for interleukin (IL)-9, IL-13, IL-5, IL-4, IL-6, lymphotoxin α, and granulocyte-macrophage colony-stimulating factor-cytokines involved with antibody formation and type 2 immune responses. The relationship of this signal to transplant outcomes and impact of adjunctive receptor blockade requires additional investigation.
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
Funders: National Kidney Foundation, American Society of Nephrology, Koch Foundation, 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, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: G3411500967, G3756175955, Translational Research Training in Pediatric Nephrology, Development of Transplant Strategies Uniquely Responsive to the Needs of Children, The Impact of Epstein Barr Virus Infection on the Immune Response in Pediatric Transplant Recipients, G562934659, G8187534011, G9000252277, Innate-Adaptive Immunoregulation in Liver Transplant Ischemia/Reperfusion Injury, Targeting the transcriptional co-activators YAP and TAZ with statins to prevent solid organ transplant rejection by HLA donor specific antibodies, Systems Epigenomics of Persistent Bloodstream Infection, 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: W4413014872