ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

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

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO845

Neutrophil Degranulation in Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Powell, David W., University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Brady, Makayla, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Tandon, Shweta, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Lightman, Rebecca, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Short, Nicholas A., University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Rane, Madhavi J., University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Barati, Michelle T., 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 accumulating evidence for neutrophil involvement in lupus nephritis (LN). Neutrophils are recruited into glomeruli following immune complex deposition, where they release toxic antimicrobial agents and immune regulatory molecules from preformed granules. Our previous reports with mice and cultured cells show that neutrophil granule proteins contribute to immune complex-mediated glomerular injury and directly injure podocytes and glomerular endothelial cells. The aim of this study is to investigate the contribution of neutrophil degranulation in human LN.

Methods

Levels of twelve neutrophil granule proteins were measured in urine and serum from 10 LN patients with active disease and 8 healthy controls (HC) using an antibody-based array and ELISA validations. Flow cytometry was used to measure markers of secretory, specific, and azurophilic granule release in untreated neutrophils from LN patients and HC and in HC neutrophils in response to LN patient or HC serum.

Results

Six of the targeted granule proteins (neutrophil elastase, olfactomedin-4, lactoferrin, a-1AG, MMP-9, and cathelicidin) were significantly elevated in urine from LN patients, and neutrophil elastase was the only protein higher in LN serum. Degranulation of all granule subsets were significantly enhanced in untreated neutrophils from LN patients compared to HC. Serum from active LN patients, but not HC serum, significantly activated granule release in HC neutrophils.

Conclusion

Our findings suggest that enhanced neutrophil degranulation could play a role in LN pathology and that urine measurement of neutrophil granule proteins could serve as markers of kidney inflammation.

Funding

  • NIDDK Support