Cytokine Profiles Associated With Angiotensin II Type 1 Receptor Antibodies

Abstract

Introduction: Angiotensin II type 1 receptor antibody (AT1R-Ab), is a non–human leukocyte antigen (HLA) antibody implicated in poor renal allograft outcomes, although its actions may be mediated through a different pathway than HLA donor-specific antibodies (DSAs). Our aim was to examine serum cytokine profiles associated with AT1R-Ab and distinguish them from those associated with HLA DSA in serially collected blood samples from a cohort of pediatric renal transplant recipients. Methods: Blood samples from 65 pediatric renal transplant recipients drawn during the first 3 months posttransplant, at 6, 12, and 24 months posttransplant, and during suspected episodes of kidney transplant rejection were tested for AT1R-Ab, HLA DSA, and a panel of 6 cytokines (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-8, IL-1β, IL-6, and IL-17). Associations between antibodies and cytokines were evaluated. Results: AT1R-Ab, but not HLA DSA, was associated with elevations in TNF-α, IFN-γ, IL-8, IL-1β, IL-6, and IL-17. This relationship remained significant even after controlling for relevant clinical factors and was consistent across all time points. In contrast to HLA DSA, AT1R-Ab was associated with elevations in vascular inflammatory cytokines in the first 2 years posttransplant. Conclusions: This profile of vascular cytokines may be informative for clinical monitoring and designing future studies to delineate the distinct pathophysiology of AT1R-Ab–mediated allograft injury in kidney transplantation. Keywords: angiotensin II type 1 receptor antibody, cytokine, human leukocyte antigen donor-specific antibody, pediatric nephrology, transplantation