Endothelin-1 Type A Receptor Antibodies Are Associated with Elevated Il-8, Arteritis and Decline in Renal Function in Pediatric Renal Transplant Recipients
1University of California, Los Angeles, Los Angeles, CA
2Duke University, Durham, NC.
Meeting: 2018 American Transplant Congress
Abstract number: 59
Keywords: Antibodies, Kidney transplantation, Pediatric, Renal injury
Session Information
Session Name: Concurrent Session: Kidney: Pediatrics - 1
Session Type: Concurrent Session
Date: Sunday, June 3, 2018
Session Time: 2:30pm-4:00pm
Presentation Time: 3:30pm-3:42pm
Location: Room 3AB
Background: We have recently shown that the non-HLA antibody, AT1R-Ab, is prevalent and associated with poor outcomes in pediatric kidney transplant recipients (KTRs). The prevalence and significance of other G-protein coupled receptor non-HLA antibodies in pediatric KTRs remains unclear. We aimed to determine the clinical impact of endothelin-1 type A receptor antibody (ETAR-Ab) in pediatric KTRs.
Methods: 65 pediatric patients were monitored for 2 years after transplantation from August 2005 to November 2014. ETAR-Ab (ELISA), AT1R-Ab (ELISA), HLA DSA (Luminex), and TNF-α, IL-1β, IL-8, IFN-γ, IL-17, IL-6 (Luminex) were measured at 6 months (m), 12m, and 24m post-transplant and during episodes of rejection. Based on a receiver operating curve analysis, > 10 and >17 units/ml was considered positive for ETAR-Ab and AT1R-Ab and >1000 MFI was considered positive for HLA DSA. Biopsies were performed at 6m, 12m, and 24m post-transplant per protocol and for clinical suspicion of rejection and evaluated by 2013 Banff criteria. Clinical outcomes and renal function was serially assessed (MDRD for >18 and updated Schwartz Equation for <18 years old).
Results: The prevalence of patients positive for ETAR-Ab at any time point was 32% (21/65). ETAR-Ab was associated with AT1R-Ab (p<0.001), but not HLA DSA. AT1R-Ab was present in all patients who had ETAR-Ab. ETAR-Ab was associated with decrease in eGFR by 50% (p=0.045) and arteritis on biopsy (p=0.011), but not allograft loss, rejection, or hypertension (Figure 1a). Furthermore, patients positive for ETAR-Ab had higher median levels of IL-8 (p=0.003, Figure 1b).
Conclusions: In pediatric KTRs, ETAR-Ab in combination with AT1R-Ab may promote vascular inflammation, leading to allograft dysfunction. Treatment with dual blockade may mitigate vascular injury and improve clinical outcomes.
CITATION INFORMATION: Pearl M., Grotts J., Rossetti M., Zhang Q., Weng P., Reed E., Tsai Chambers E. Endothelin-1 Type A Receptor Antibodies Are Associated with Elevated Il-8, Arteritis and Decline in Renal Function in Pediatric Renal Transplant Recipients Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Pearl M, Grotts J, Rossetti M, Zhang Q, Weng P, Reed E, Chambers ETsai. Endothelin-1 Type A Receptor Antibodies Are Associated with Elevated Il-8, Arteritis and Decline in Renal Function in Pediatric Renal Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/endothelin-1-type-a-receptor-antibodies-are-associated-with-elevated-il-8-arteritis-and-decline-in-renal-function-in-pediatric-renal-transplant-recipients/. Accessed May 17, 2025.« Back to 2018 American Transplant Congress