N-Glycans and Glycosphingolipids as Biomarkers and Modulators of Lupus Nephritis
Abstract
The two goals of the grant are to 1) identify urine biomarkers of disease and therapeutic response in lupus nephritis (LN) patients, and 2) determine the pathophysiologic roles of glycosphingolipid (GSL) metabolism in renal cells. With respect to goal number 1, we have identified, obtained, processed, and begun to measure N-glycosylated proteins and glycosphingolipids in 176 LN patients, 116 lupus patients without nephritis, and 114 healthy controls (HC). In addition, we measured GLSs and N-glycosylated proteins in urine and serum from a separate set of 20 LN patients and 20 healthy controls (HC) demonstrating extensive altered N-glycosylation and increased GSLs in the urine of LN patients and evaluated associations with biologic sex. With respect to goal number 2, serum from these 40 individuals was used to stimulate human renal mesangial cells (hRMCs), demonstrating that the biologic sex of the cells had a significant impact on their proinflammatory response and corresponded with GSL levels. These results are included in a manuscript currently under review. We also collected extensive preliminary data over the past year in hRMCs and co-cultures of hRMCs and renal glomerular endothelial cells (hRGECs) analyzing cellular responses to external stimuli when reducing GSL levels using the drug eliglustat.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1229005
Entities
People
- Aaron Angerstein
- Bethany Wolf
- Danielle Beaufort
- James Oates
- Richard Drake
- Sandra Mungaray
- Tamara K Nowling
Organizations
- Medical University of South Carolina