Targeting IRF5 Activation for the Treatment of Lupus
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Steven M. Draikiwicz, MD, Saurav De, Eugenio Capitle, MD, Betsy Barnes, PhD
Rationale: Systemic Lypus Erythematosus is characterized by increased auto-antibody production.  The molecular mechanisms involved in lupus onset however, have not been clearly defined.  Several transcription factors have been identified to strongly correlate with disease onset.  One such transcription factor is interferon regulatory factor 5 (IRF5).  Polymorphisms in the IRF5 gene have been one of the most strongly associated factors for the onset of SLE.   The focus of our work has been to stratify the impact of smoking on the nuclear translocation of IRF5 within the SLE population.

Methods: We have currently recruited 10 patients for analysis of IRF5 expression.  8 subjects were controls and 2 were in the experimental arm.  Controls are defined as patients with active lupus activity who do not smoke whereas patients in the experimental arm are patients with active lupus who are smokers.  20mL of  peripheral blood was drawn from each subject and IRF5 expression was analyzed utilizing Imaging Flow Cytometry with gating on monocyte and B cell subpopulations.

Results: Non-smoking SLE patients showed a 35% translocation of IRF5 in Naive B Cells, 20% translocation in plasmablasts and 28% in CD14+ monocytes.  Smoking patients with SLE showed 30%  translocation of IRF5 in Naive B Cells, 15% translocation in Plasmablasts and 35% in CD14+ monocytes.  The difference of IRF5 translocation between non-smoking and smoking SLE patients was not significant.

Conclusions: This is preliminary data which currently suggests smoking does not cause changes in levels of IRF5 translocation.  As this is preliminary data, results will be updated when further data becomes available.