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Biomarkers for Disease Flare by Emily Baechler Gillespie

Biomarkers for Disease Flare by Emily Baechler Gillespie






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    Biomarkers for Disease Flare by Emily Baechler Gillespie Biomarkers for Disease Flare by Emily Baechler Gillespie Presentation Transcript

    • 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
    • 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”
    • 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
    • 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
    • Is there a fingerprint for lupus flare?
      Disease activity
      6 mo.
      9 mo.
      3 mo.
      12 mo.
    • 172 proteins measured in 30 SLE patients and 15 controls
    • 7 proteins measured in 81 SLE patients (longitudinal visits)
    • 4 proteins measured in 267 SLE patients (longitudinal visits)
    • 4 proteins measured in 373 SLE patients (single visits)
      Same proteins, more focus on clinical utility
    • 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
    • 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
    • CK-high patients are at increased risk for future flare
      Bauer et al., Arthritis Rheum 2009
    • 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
    • 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)