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Differential Inflammatory Vascular Cytokine Profiles Associated with Angiotensin II Type 1 Receptor Antibodies and Human Leukocyte Antibodies in Pediatric Renal Transplantation


Background: Both human leukocyte antigen donor specific antibodies (HLA DSA) and non-HLA autoantibodies have been implicated in antibody-mediated rejection (AMR), allograft dysfunction, and allograft failure in kidney transplantation. Angiotensin II type 1 receptor antibody (AT1R-Ab), is a non-HLA antibody implicated in poor renal allograft outcomes, although its actions may be mediated through a different mechanistic pathway than HLA DSA.

Objective: 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: 65 pediatric kidney transplant patients were monitored for 2 years post-transplant. Blood samples from early post-transplant and at 6, 12, and 24 months post-transplant and during suspected episodes of kidney transplant rejection were tested for AT1R-Ab, HLA DSA, and a panel of 6 cytokines (TNF-α, IFN-γ, 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 when controlling for relevant clinical factors and potential confounders, and was consistent across time points.

Conclusion: In contrast to HLA DSA, AT1R-Ab was associated with elevations in vascular inflammatory cytokines in the first 2 years post-transplant. This profile of vascular cytokines may be informative for designing further studies to understand the distinct pathophysiology of AT1R-Ab mediated allograft injury in kidney transplantation.

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