Dubois lecturer to explore immune system phenotyping to identify novel biomarkers

The diagnosis and treatment of lupus, like many other autoimmune diseases, is imprecise at best. Improved understanding of immune system dysregulation will help researchers develop and validate reliable biomarkers to assist clinicians in positively identifying lupus, evaluating treatment alternatives, and assessing treatment results.

“What we have now is an increasingly clear description of the major features of immune dysregulation in lupus,” said Deepak Rao, MD, PhD, Assistant Professor of Medicine, Harvard Medical School, and Co-Director of the Brigham and Women’s Hospital Center for Cellular Profiling. “We are analyzing samples from patients in real time to generate foundational data supporting the case for clinically actionable biomarkers. We’re not yet at the stage where you have a test you can order in clinic, but we have a direct path to transform better understanding of immune dysregulation into a useful clinical tool.”

Dr. Rao will explore the cutting edge of translational research into immune dysregulation in lupus during the Edmund L. Dubois, MD, Memorial Lecture on Saturday, November 12, from 12:30–1 p.m. ET, in Terrace Ballroom IV of the Pennsylvania Convention Center. Meeting participants have the option to attend the lecture in person or on the meeting website via livestream, or to view the lecture on demand.

Simply recognizing the presence of lupus and confirming a diagnosis is challenging using clinical features alone, Dr. Rao noted. The clinical presentation of lupus is an unpredictable collection of signs and symptoms that result from different types and degrees of immune system dysregulation. This heterogeneity makes it difficult to predict clinical response to management approaches and to assess possible treatment effects.

Dr. Rao’s lab and others are evaluating lupus by way of changes in the different populations of immune cells circulating in patients’ blood. The goal is to identify and characterize clearly altered or abnormal phenotypes of circulating T cell and B cell phenotypes in lupus patients. Other projects are exploring phenotypes of altered immune cell populations in the kidneys and urine of patients with lupus nephritis.

“We are looking for guideposts of what immune dysregulation in lupus looks like,” he explained. “One of the major purposes is to develop these markers into metrics we can use clinically to measure how active the adaptive immune system is in patients sitting in front of us in clinic as we try to make decisions about which treatments to use and whether or not to adjust therapy.”

An important element in developing clinically actionable biomarkers is to characterize changes in immune cell populations in response to mycophenolate mofetil versus hydroxychloroquine versus high-dose steroids. Another element is tracing the arc of immune system dysregulation from suspected lupus to clinical disease.

“We are asking how early we can see phenotypic changes in individuals who have incomplete or suspected lupus, those who have positive antibody tests but don’t fulfill the clinical criteria for lupus,” Dr. Rao said. “Do they have some of those same features of immune dysregulation we see in patients with lupus? The hope is to develop a diagnostic biomarker to help recognize the presence or absence of disease. This is a tangible example of the value of understanding immune dysregulation and making the transition into clinical practice.”