Biomarkers for Disease Flare by Emily Baechler Gillespie

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Biomarkers for Disease Flare by Emily Baechler Gillespie

  1. 1. Genetics and Flare:Biomarkers for Disease Activity in SLE<br />Emily Baechler Gillespie, Ph.D.<br />University of Minnesota Department of Medicine<br />Division of Rheumatic and Autoimmune Diseases<br />
  2. 2. Why Biomarkers for Disease Activity in SLE?<br />Patient monitoring and management: Improve on existing lab tests<br />Predicting risk of future activity: Limit or prevent flares<br />Evaluating response to therapy: Promote drug development, “tailored therapy”<br />
  3. 3. Serum Protein Biomarkers for Systemic Lupus<br />Identify proteins in the blood that are markers for lupus disease activity<br />Measure these proteins over time in a large group of lupus patients<br />Assess the ability of the proteins to predict changes in disease activity<br />Provide foundation for development of a new clinical test for SLE<br />
  4. 4. Interferon signature: What is it?<br />Interferon (IFN): Part of normal immune response<br />IFN signature: Some SLE patients have an over-active IFN pathway<br />Identified by measuring IFN-inducible mRNA transcripts and proteins<br />A fingerprint for severe SLE<br />
  5. 5. Is there a fingerprint for lupus flare?<br />Disease activity<br />6 mo.<br />9 mo.<br />3 mo.<br />Enroll<br />12 mo.<br />Time<br />
  6. 6. 172 proteins measured in 30 SLE patients and 15 controls <br />
  7. 7. 7 proteins measured in 81 SLE patients (longitudinal visits)<br />
  8. 8. 4 proteins measured in 267 SLE patients (longitudinal visits)<br />
  9. 9. 4 proteins measured in 373 SLE patients (single visits)<br />Same proteins, more focus on clinical utility<br />
  10. 10. Results of LRI-Funded Work<br />IFN-regulated chemokines<br />The ‘traffic cops’ of the immune system<br />Chemokine levels in SLE:<br />Higher in active vs. inactive SLE<br />Correlate with SLE activity, rising at flare and falling with remission<br />A better indicator of lupus activity than standard clinical lab tests<br />Bauer et al., PLoS Med 2006 <br />
  11. 11. Do elevated chemokine levels predict future flare?<br />Identify patients with mild or inactive disease44 with high chemokine levels (CK-high) 108 CK-intermediate 72 CK-low <br />Compare frequency of flares during one year of clinical follow-up<br />
  12. 12. CK-high patients are at increased risk for future flare<br />Bauer et al., Arthritis Rheum 2009<br />
  13. 13. Ongoing Studies<br />Could this be the basis for a new clinical test for lupus?<br />Opportunity to try therapeutic intervention<br />Could this test identify people who are at risk for future development of lupus? <br />New funding to test ANA+ subjects <br />Potential to identify patients who are most likely to benefit from new drugs<br />
  14. 14. Acknowledgments<br />University of MN<br />Jason Bauer, PhD<br />Hatice Bilgic, PhD<br />Mehrnaz Hojjati, MD <br />Thearith Koeuth<br />Joe Wilson<br />Carolyn Meyer<br />ABCoN Collaborators<br />Tim Behrens, MD(Genentech)<br />Peter Gregersen, MD (Feinstein Institute)<br />Michelle Petri, MD (Johns Hopkins)<br />

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