Abstract: FR-PO1124
Role of Interferon-y Associated Chemokines and FOXP3+ T Cells in BK Virus Nephropathy
Session Information
- Transplantation: Basic
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1901 Transplantation: Basic
Authors
- Shrestha, Sneha, Weill Cornell Medical College, New York, New York, United States
- Abuhelaiqa, Essa, Weill Cornell Medical Center, New York, New York, United States
- Snopkowski, Catherine, Weill Cornell Medical College, New York, New York, United States
- Lee, John Richard, Weill Cornell Medical Center, New York, New York, United States
- Salvatore, Steven, Weill Cornell Medical College, New York, New York, United States
- Lubetzky, Michelle L., Division of Nephrology and Hypertension, New York, New York, United States
- Muthukumar, Thangamani, Weill Cornell Medical College, New York, New York, United States
- Seshan, Surya V., Weill Cornell Medical Center, New York, New York, United States
- Suthanthiran, Manikkam, Weill Cornell Medical College, New York, New York, United States
- Dadhania, Darshana, Weill Cornell Medical College, New York, New York, United States
Background
BKV reactivation has been associated with increased expression of interferon-y (IFNy) induced chemokines and increased levels of granzyme B, cytotoxic T cell molecule. Histological findings of BK virus nephropathy (BKVN) have been compared to those with acute cellular rejection (ACR) but the role of FOXP3 has not been studied. We hypothesized that heightened expression of IFNy associated chemokines and lower expression of FOXP3 would be prognostic of 3-year outcomes in BKVN.
Methods
To address this hypothesis, we studied absolute mRNA copies of MIG, IP-10, CD3, granzyme B, FOXP3 and 18SrRNA in biopsy matched urine cell pellets of 53 BKVN and 33 ACR patients using a standard curve method in real-time quantitative PCR assay. Continuous variables were compared using Mann-Whitney test and logistic regression was used to determine if urine mRNAs were predictive of graft loss in BKVN patients.
Results
We found that urinary cell mRNA for interferon-y inducible chemokines IP-10 was higher and mRNAs for CD3, GB and FOXP3 were lower in BKVN cohort compared to ACR cohort. Ratio of IP-10/CD3 mRNA in urinary cells was significantly higher in BKVN cohort versus ACR cohort. Urinary cell mRNA for IP-10, MIG and GB were associated with increased risk of 3 year graft loss.
Conclusion
We conclude that BKVN is associated with increased levels of IP-10 and lower levels of CD3 as compared to ACR and the ratio of IP10/CD3 mRNA can be used to distinguish inflammation associated with BKVN from that of ACR. Urinary cell mRNA levels of IFNy associated chemokines are associated with 3-year graft loss.