Kidney Week

Abstract: FR-PO1179

Differential Cytokine Profiles for Non-Human Leukocyte Antigen (Non-HLA) and HLA Antibodies in Pediatric Kidney Transplantation

Session Information

• Pediatric Nephrology - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1600 Pediatric Nephrology

Authors

• Pearl, Meghan, UCLA, Los Angeles, California, United States

Meghan Pearl,

• Grotts, Jonathan, UCLA, Los Angeles, California, United States

Jonathan Grotts,

• Rossetti, Maura, UCLA, Los Angeles, California, United States

Maura Rossetti,

• Zhang, Qiuheng Jennifer, UCLA, Los Angeles, California, United States

Qiuheng Jennifer Zhang,

• Weng, Patricia L., UCLA, Los Angeles, California, United States

Patricia L. Weng,

• Elashoff, David, UCLA, Los Angeles, California, United States

David Elashoff,

• Reed, Elaine F., UCLA, Los Angeles, California, United States

Elaine F. Reed,

• Tsai, Eileen W., Duke University, Durham , North Carolina, United States

Eileen W. Tsai,

Background

The inflammatory profiles associated with human leukocyte antigen (HLA) and 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 outcomes in pediatric KTRs. We aimed to compare inflammatory profiles of AT1R-Ab, ETAR-Ab, and HLA donor specific antibodies (DSA) in pediatric KTRs.

Methods

233 blood samples from 65 pediatric KTRs were analyzed. ETAR-Ab (ELISA), AT₁R-Ab (ELISA), HLA DSA (Luminex), and TNF-α, IL-1β, IL-8, IFN-γ, IL-17, IL-6 (Luminex) were measured in blood samples taken at 6 months (m), 12m, and 24m post-transplant and during episodes of rejection. Based on a receiver operating curve analysis, > 10 and >17 units/ml was considered positive for ETAR-Ab and AT₁R-Ab and >1000 MFI was considered positive for HLA DSA.

Results

HLA DSA, AT1R-Ab, and ETAR-Ab were positive in 25 (11%), 92 (40%), and 50 (22%) of samples respectively. 96% of samples positive for ETAR-Ab also had AT1R-Ab. All three antibodies were associated with elevations in IL-8 while AT1R-Ab was associated with elevations in all 6 cytokines (Table 1).

Conclusion

AT1R-Ab is associated with a distinct inflammatory profile compared to HLA DSA or ETAR-Ab in the first 2 years post-transplant. Further studies are needed to understand the distinct mechanisms of HLA vs. non-HLA antibody mediated allograft injury.

Funding

• Private Foundation Support