Biomarkers for Disease Flare by Emily Baechler Gillespie

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.
Enroll
12 mo.
Time

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)

Biomarkers for Disease Flare by Emily Baechler Gillespie

by LupusNY on Sep 07, 2010

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Biomarkers for Disease Flare by Emily Baechler Gillespie Presentation Transcript