Glycosphingolipids as Therapeutic Targets and Biomarkers of Lupus Nephritis
Abstract
In general, the initiating events of lupus are universally accepted to involve a genetic predisposition and an environmental trigger. Our data indicates that increased glycosphingolipid (GSL) levels in the kidney and urine of lupus mice and patients with nephritis is due to local renal increases in GSL metabolism following immune complex deposition. Altered GSL metabolism is unlikely to be a causative event in lupus nephritis, but GSLs likely play a pathogenic role in disease progression and are clear biomarker targets to monitor treatment efficacy and disease progression. Long-term goal and scope of the research includes targeting key molecules leading to reduction of renal damage to slow or prevent the progression of nephritis in lupus and other chronic kidney diseases, a major health concern in the Veteran population. The purpose (short-term goals) of this project is to 1) identify early urine biomarkers that will allow for earlier intervention to identify patients who fail therapy and/or prevent flares in lupus patients; and 2) demonstrate that the GSL catabolic pathway is a pathophysiological mechanism and novel target for therapeutic intervention in LN with relevance to other inflammatory kidney diseases. Our studies will have a profound impact on patients and the field of lupus by identifying specific mediators and biomarkers of renal pathology and opening up additional avenues of investigation in LN with applications to other renal diseases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1086244
Entities
People
- James Oates
- Jessalyn Rodgers
- Kamala Sundararaj
- Richard Drake
- Tamara K Nowling
- Wolf Bethany
Organizations
- Medical University of South Carolina