Biomarkers for Disease Flare by Emily Baechler Gillespie
1. Genetics and Flare:Biomarkers for Disease Activity in SLE Emily Baechler Gillespie, Ph.D. University of Minnesota Department of Medicine Division of Rheumatic and Autoimmune Diseases
2. Why Biomarkers for Disease Activity in SLE? Patient monitoring and management: Improve on existing lab tests Predicting risk of future activity: Limit or prevent flares Evaluating response to therapy: Promote drug development, “tailored therapy”
3. Serum Protein Biomarkers for Systemic Lupus Identify proteins in the blood that are markers for lupus disease activity Measure these proteins over time in a large group of lupus patients Assess the ability of the proteins to predict changes in disease activity Provide foundation for development of a new clinical test for SLE
4. Interferon signature: What is it? Interferon (IFN): Part of normal immune response IFN signature: Some SLE patients have an over-active IFN pathway Identified by measuring IFN-inducible mRNA transcripts and proteins A fingerprint for severe SLE
5. Is there a fingerprint for lupus flare? Disease activity 6 mo. 9 mo. 3 mo. Enroll 12 mo. Time
9. 4 proteins measured in 373 SLE patients (single visits) Same proteins, more focus on clinical utility
10. Results of LRI-Funded Work IFN-regulated chemokines The ‘traffic cops’ of the immune system Chemokine levels in SLE: Higher in active vs. inactive SLE Correlate with SLE activity, rising at flare and falling with remission A better indicator of lupus activity than standard clinical lab tests Bauer et al., PLoS Med 2006
11. Do elevated chemokine levels predict future flare? Identify patients with mild or inactive disease44 with high chemokine levels (CK-high) 108 CK-intermediate 72 CK-low Compare frequency of flares during one year of clinical follow-up
12. CK-high patients are at increased risk for future flare Bauer et al., Arthritis Rheum 2009
13. Ongoing Studies Could this be the basis for a new clinical test for lupus? Opportunity to try therapeutic intervention Could this test identify people who are at risk for future development of lupus? New funding to test ANA+ subjects Potential to identify patients who are most likely to benefit from new drugs
14. Acknowledgments University of MN Jason Bauer, PhD Hatice Bilgic, PhD Mehrnaz Hojjati, MD Thearith Koeuth Joe Wilson Carolyn Meyer ABCoN Collaborators Tim Behrens, MD(Genentech) Peter Gregersen, MD (Feinstein Institute) Michelle Petri, MD (Johns Hopkins)
