Abstract: PO2182
Inflammatory Profile Associated with Non-HLA Antibodies to G-Protein Coupled Receptors in Pediatric Kidney Transplant Recipients
Session Information
- Transplantation: Clinical - Noninvasive Biomarkers, Immune Regulation, and Fascinomas
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1902 Transplantation: Clinical
Authors
- Pearl, Meghan, University of California Los Angeles, Los Angeles, California, United States
- Chen, Lucia, University of California Los Angeles, Los Angeles, California, United States
- Vangala, Sitaram, University of California Los Angeles, Los Angeles, California, United States
- Weng, Patricia L., University of California Los Angeles, Los Angeles, California, United States
- Chambers, Eileen Tsai, Duke University School of Medicine, Durham, North Carolina, United States
- Elashoff, David, University of California Los Angeles, Los Angeles, California, United States
- Reed, Elaine F., University of California Los Angeles, Los Angeles, California, United States
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).
Conclusion
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