Inflammatory Profile Associated with Non-HLA Antibodies to G-Protein Coupled Receptors in Pediatric Kidney Transplant Recipients

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Background: The inflammatory profiles associated with non-HLA antibodies to G-protein coupled receptors in kidney transplant recipients (KTRs) are unknown. We have recently shown that angiotensin II type 1 receptor antibody (AT1R-Ab) and Endothelin-1 Type A receptor antibody (ETAR-Ab) are prevalent and associated with poor clinical outcomes and elevations in TNF-α, IL-1β, IL-8, IFN-γ, IL-17, and IL-6 in pediatric KTRs. We aimed to expand this analysis by examining the association between these non-HLA antibodies and a broad panel of inflammatory markers in a different cohort of pediatric KTRs. Methods: 157 blood samples from 35 pediatric KTRs followed for 2 years post-transplant were analyzed. ETAR-Ab (ELISA), AT1R-Ab (ELISA), and 38 cytokines (Luminex, Table 1) were measured in blood samples taken at 6 months (m), 12m, and 24m post-transplant and during episodes of rejection. Based on previous receiver operating curve analysis, > 10 and >17 units/ml was considered positive for ETAR-Ab and AT1R-Ab. Patients were serially monitored for viral infections (CMV, EBV, and BK Virus), HLA DSA (Luminex), and rejection (protocol and indication biopsies). Results: Blood samples positive for AT1R-Ab and ETAR-Ab had elevations in 28 of 38 cytokines (Table 1). On principal component (PC) analysis, AT1R-Ab and ETAR-Ab positivity was highly associated with differences in PC1. This relationship remained significant even when controlled for potential confounders, including age, sex, rejection, viral infections, and HLA DSA status (p<0.001, Figure 1). Conclusions: AT1R-Ab and ETAR-Ab positivity is associated with a distinct inflammatory profile in pediatric KTRs in the first 2 years post-transplant. This distinct profile may help inform mechanistic studies and potentially identify new therapeutic targets to treat non-HLA associated allograft injury. Funding: Other NIH Support - NIAID, Private Foundation Support

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