Abstract: SA-PO832
Neutrophil Reactive Oxygen Species Generation and Association with Clinical Disease Markers in Lupus Nephritis
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Lightman, Rebecca, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Brady, Makayla, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Short, Nicholas A., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Tandon, Shweta, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Barati, Michelle T., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Rane, Madhavi J., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Powell, David W., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Caster, Dawn J., University of Louisville School of Medicine, Louisville, Kentucky, United States
Background
There is growing evidence for neutrophil involvement in lupus nephritis (LN). Neutrophils infiltrate the glomerulus and mediate cellular injury via granular release of toxic and immunologic molecules including reactive oxygen species (ROS). We aim to determine if LN neutrophils are more primed to produce ROS than controls and if ROS generation is associated with clinical disease features.
Methods
Neutrophils were isolated from whole blood of 16 LN patients and 6 healthy controls for use in superoxide assay. Cells were untreated, treated with fMLF, or treated with fMLF plus TNF-α. fMLF is a positive activator and TNF-α primes the response.
Clinical data were obtained from Epic: UPCR, C3, C4, anti-dsDNA, and creatinine. eGFR was calculated using the 2021 CKD-EPI creatinine equation. Control data were not available.
Results
ROS generation was compared by treatment group and patient status using mixed-effects analysis with Šídák multiple comparisons test. For fMLF alone, LN neutrophils produced more ROS than controls (p=0.0028). Fold change in ROS was calculated for untreated to fMLF as well as untreated to fMLF plus TNF-α priming, and the difference was compared using unpaired T-tests. For LN, fold change from untreated did not differ between fMLF and fMLF plus TNF-α (p=0.6221). However, fold change from untreated to fMLF plus TNF-α was greater in controls (p=0.0041).
Multiple linear regression was used to determine if clinical data is associated with ROS generation in LN. For untreated, anti-dsDNA (p=0.0439) and eGFR (p=0.0318) were associated. For fMLF, C4 (p=0.0286) was associated. For fMLF plus TNF-α, UPCR (p=0.0210), C3 (p=0.0199), C4 (p=0.0025), creatinine (p=0.0325), and eGFR (p=0.0130) were associated. Finally, anti-dsDNA was associated with fold change in ROS for untreated to fMLF (p=0.0136) and untreated to fMLF plus TNF-α (p=0.0152).
Conclusion
LN neutrophils had a greater response to fMLF than controls. This suggests the possibility of endogenous primers in LN serum, which may play a role in LN pathogenesis and affect neutrophils beyond ROS generation.
Discussion and investigation are ongoing regarding the utility of clinical markers in LN as well as potential new markers. Using clinical data to predict underlying disease may improve future treatments.
Funding
- NIDDK Support