Competition Catalyst Grant 2018-19

Application Metrics:  2/8 Applications Funded

Principal Investigator:  Dr. Joan Wither

Institution:  University Health Network

Project Title:  Using CyTOF to dissect the interplay between Type I interferon and autoantibody production in Systemic Lupus Erythematosus

Funding Received:  $35,000 Awarded

Project Lay Summary:  In SLE antibodies are mistakenly produced against molecules that are part of the body, such as DNA and other proteins found in the nuclei of cells. These anti-nuclear antibodies (ANAs) deposit in the organs where the cause inflammation resulting in damage. SLE follows an unpredictable course, with the majority of patients undergoing remission and exacerbation. Currently, the immune mechanisms that distinguish periods of disease activity from inactivity are unknown, however the correlation between disease activity and levels of ANA as well as antibody secreting cells suggests that flares result from increased antibody production. Recently a novel B cell population, called ABCs, was identified that represent activated B cells that are poised to become antibody secreting cells. Using a mouse model of lupus we showed that administration of interferon, at levels similar to those seen in human lupus, was sufficient to promote development of ABCs. This led us to wonder whether one of the reasons that SLE patients with high levels of interferon have more severe disease is that interferon changes the function of their B cells making them more prone to become ABCs and consequently more likely to develop into antibody secreting cells. To address this question we plan to use a state-of-the art experimental technique, CyTOF, to examine the B cells in active and inactive SLE patients to determine whether they have been exposed to interferon and whether it has altered their function. If so, our experiments would support the use of interferon targeted therapies for flare prevention.