Abstract: FR-PO193
Soluble Interleukin 2 Receptor as a Potential Biomarker for Immune Checkpoint Inhibitor Nephritis (ICI-AIN)
Session Information
- Onconephrology: Clinical and Research Advances - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Wang, Qiyu, Massachusetts General Hospital, Boston, Massachusetts, United States
- Seethapathy, Harish Shanthanu, Massachusetts General Hospital, Boston, Massachusetts, United States
- Smith, Rex Neal, Massachusetts General Hospital, Boston, Massachusetts, United States
- Rosales, Ivy A., Massachusetts General Hospital, Boston, Massachusetts, United States
- Colvin, Robert B., Massachusetts General Hospital, Boston, Massachusetts, United States
- Herrmann, Sandra, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Farmer, Jocelyn, Massachusetts General Hospital, Boston, Massachusetts, United States
- Sise, Meghan E., Massachusetts General Hospital, Boston, Massachusetts, United States
Background
Soluble interleukin 2 receptor (sIL-2R), a marker of T-cell activation, is used to monitor disease activity for autoimmune conditions and congenital immunodeficiencies. We hypothesize that sIL-2R may be elevated in patients with ICI-AIN and potentially serve as a diagnostic biomarker.
Methods
Retrospective cohort study of patients diagnosed with ICI-AIN (histologic or clinical diagnosis) who had sIL-2R measured as part of work-up. We prospectively enrolled 2 control cohorts: 1) Patients receiving ICIs for cancer with normal kidney function (“healthy ICI-treated controls”); 2) Patients not receiving ICIs who were hospitalized with hemodynamic acute kidney injury (AKI). Patients were excluded if they had active infection or received immunosuppression within 2 weeks of sample collection. sIL-2R levels were standardized using the fold change of the upper limit of normal (ULN) of the CLIA-certified assay. Receiver operating curve (ROC) was generated comparing sIL-2R level between “ICI-AIN” and “hemodynamic AKI controls”, and “ICI-AIN” and “healthy ICI controls”. Using archived biopsy samples, we compared IL2R-α gene expression measured by Nanostring in patients with ICI-AIN (N=22), acute tubular injury (ATI, N=9) and healthy kidney donors (N=11).
Results
sIL-2R levels were significantly higher in ICI-AIN (N=21, median 2.5 fold-ULN, IQR 1.9-3.3), compared to “healthy ICI-treated controls” (N=9, median 0.7 fold-ULN, IQR 0.5-0.9) and “hemodynamic AKI controls” (N=6, median 0.9 fold-ULN, IQR 0.7-1.1).(Figure 1)ROC analysis yielded an optimal cut-point of 1.75-fold ULN of sIL-2R for differentiating ICI-AIN and hemodynamic AKI controls, with specificity of 100% (95% CI, 61%-100%) and sensitivity of 81% (95% CI, 60%-92.3%). IL2R-α gene expression was significantly higher in kidney tissue in patients with ICI-AIN compared to ATI and healthy kidney donors.(Figure 2)
Conclusion
sIL-2R is a promising biomarker for ICI-AIN that should be validated in future studies with prospective, consecutive sampling.