NR4A Family as Markers and Mediators of B Cell Tolerance in SLE: From Antigen Discovery to Treatment
Abstract
B cells play a key role in the pathogenesis of SLE by differentiating into autoantibody-secreting plasma cells, producing inflammatory cytokines, and serving as antigen presenting cells for pathogenic T cells. SLE exhibits remarkable clinical heterogeneity for which clinicians lack adequate biomarkers. This proposal harnesses the dynamic expression pattern of the NR4A family of orphan nuclear hormone receptors to identify self-reactive B cells, and couples this with our existing and well-validated phage-display pipeline for autoAb and autoAg discovery. We intend to exploit the expression of NR4A genes to identify pathogenic self-reactive B cell clones, discover their transcriptional signature, and take advantage of our existing human peptidome phage display pipeline for autoAb and autoAg identification. We aim to perform high-throughput and comprehensive profiling of serum and CSF Abs, as well as monoclonal Abs (mAbs) derived from NR4A-expressing SLE B cells in order to identify their antigenic targets. Our long-term goals are to define new autoAbs and autoAgs in SLE that serve as biomarkers of disease subsets in SLE with prognostic and therapeutic significance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1222265
Entities
People
- Judith Ashouri
- Julie Zikherman
- Michael C Wilson
- Samuel Pleasure
Organizations
- University of California Regents