Mark Walter, PhD

University of Alabama, Birmingham AL

2015 - Target Identification, Biomarkers, Interferon, Human Lupus Biology
2010 Human Lupus Biology
2011 General Immune System Function

2015: Identifying Which Interferons Cause Lupus Symptoms

The study and what it means to patients

Our Novel Research project is using innovative technology to pinpoint which interferons, proteins that contribute to symptoms and severity of lupus, are most critical in the disease. This information may be used to develop blood tests for diagnosing and measuring the effectiveness of lupus treatments. In addition, knowing which interferons are the primary culprits gives us a target to guide the design of more precise interferon inhibitors to treat lupus.

Summary

Seventeen proteins called interferons are key contributors to lupus autoimmunity. Our research goal is to determine the levels of all of these different interferons in blood as a measure of their activity. Importantly, we are not looking at just the individual interferons, but also determining if combinations of interferons work together to cause disease. This “combinatorial analysis” will uncover clues to how the interferons work together, what effects different combinations have on patient health and ultimately identify correlations between interferons and disease activity. This information may be used to develop blood tests for biomarkers of lupus—not just for diagnosis, but to measure the effectiveness of lupus treatments.

Scientific Abstract: Single Cell Detection of IFN Signaling in Lupus Patients

The goal of this application is to measure IFNs (IFNalpha, ß, epsilon, kappa, omega and IFN gamma) binding/signaling at the single cell level in peripheral blood of SLE patients.  This will be accomplished using antibodies (Abs) that recognize IFN-receptor Signaling Complexes (IFNSCAbs), but not IFN-receptors or the IFNs alone.  We hypothesize IFNSCAbs, combined with multi-parameter flow cytometry, will provide a direct measure of IFN binding and IFN signaling on blood cell subsets.   By measuring IFN signaling in this manner, we hope to improve the correlation between IFN activity/crosstalk and clinical disease parameters.  These studies could allow the use of IFN as a biomarker to assess SLE disease activity, which would have broad impact on patient monitoring and assist in characterizing novel SLE therapies.