ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO2182

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

Session Information

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