November 19, 2020
The Lupus Research Alliance supported an impressive number — 30+ — of studies presented at ACR Convergence 2020, this year’s meeting of the American College of Rheumatology. Each year, researchers are selected to share their discoveries in talks and poster sessions, allowing medical professionals to keep up to date with the latest discoveries, clinical trials that could benefit their patients and potential treatments in development.
The LRA-funded studies chosen for presentation at ACR cover a wide breadth of research, from looking at the genetic causes of lupus to exploring the immune system’s role in the development of lupus nephritis. Together, these studies identified several new therapeutic targets that could ultimately treat lupus nephritis as well as SLE. Following are just a few highlights of the studies that LRA researchers presented:
Factors that Influence Participation in Clinical Trials
Clinical trials are necessary for the approval of new drugs that can improve health outcomes for lupus patients. However, it is unclear what factors are most important to patients when they decide whether or not to participate in clinical trials. The LRA, in conjunction with the Lupus Foundation of America and the Lupus and Allied Diseases Association, funded a survey to understand learn why patients with lupus participate in clinical trials. Dr. Giya Harry of the Wake Forest School of Medicine studied the responses from 2,100 patients. She found that patients who had been ill with lupus for a long time or who had co-existing autoimmune disorders were more likely to take part in clinical trials. Unlike many studies, this one found that African-American and Hispanic patients were more likely to participate in clinical trials than Caucasians. These data may help researchers increase the participation of African-American and Hispanic patients in lupus clinical trials. See Abstract
Discovering the Genetic Causes of Lupus
Lupus is more common and more likely to lead to severe disease in African-American patients compared to European-American patients. To understand the role of genetics in this process, University of Pittsburgh doctoral student Patrick Coit and his advisor Dr. Amr Sawalha looked at changes in the genetic material (DNA) of African-American lupus patients over several years. Within immune cells known as neutrophils, the researchers discovered two genes that only switch on during periods of severe disease. The discovery of these genes may lead to new ways to monitor lupus disease activity in African-American patients. See Abstract
Immune cells known as B cells are also important contributors to the development of lupus. During lupus, some B cells produce proteins called auto-antibodies that harm healthy human cells. However, it is unclear what causes these B cells to develop and mature. To understand this process, Long School of Medicine researcher Dr. Paolo Casali studied genes important for B cell development. He found that glucose (sugar) is important for auto-antibody producing B cells to develop. He identified a gene called SIRT-1 as an important regulator of auto-antibody producing B cells which could be a new target for developing medicines for lupus.
The Role of Gut Bacteria in Lupus
A previous study of lupus patients identified the bacterium Ruminococcus gnavus as part of the microbiota in the intestines of patients with active lupus nephritis. However, it was unclear how the number of this bacteria changes within individual lupus patients over time. To address this question, Dr. Gregg Silverman, a Professor at NYU Grossman School of Medicine, measured the amount of Ruminococcus gnavus in 16 lupus patients at many points in time. Dr. Silverman found that lupus disease severity went up with an increase in Ruminococcus gnavus. However, it is still unclear whether Ruminococcus gnavus increases disease severity or if severe lupus helps increase Ruminococcus gnavus. If follow-up studies find that Ruminococcus gnavus increases disease severity, the door will be opened for lupus treatments that target this bacterium. See Abstract
Two studies presented discoveries about the role of the immune system in the development of lupus nephritis, a complication of lupus affecting kidney function.
Mouse models of lupus nephritis are useful to identify and test new potential treatments. But it is not always clear whether these models reflect the disease process in human patients. In two presentations, Harvard University researcher Dr. Paul Hoover shared his research comparing the immune cells of mice and humans. Focusing specifically on kidney immune cells, Dr. Hoover looked for similarities between cell populations found between the mice and humans. He found that most types of kidney immune cells found in humans were also present in mice with lupus nephritis. These data support research using mouse models to discover how kidney immune cells cause lupus nephritis. See Abstract
In another talk, University of Pittsburg researcher Dr. Jeremy Tilstra described the characteristics of kidney immune cells found in mice with lupus nephritis. Dr. Tilstra studied how immune cells called T cells cause kidney damage among mice with lupus nephritis. He saw that while some T cells in the kidney were causing inflammation, most T cells were inactive and not contributing to tissue damage. Further analysis suggested that active T cells entered the kidneys from the blood, caused damage, and then quickly became inactive. These findings help define the T cells that are contributing to tissue damage in the kidney, and suggest that these cells may be a good target for future therapeutic approaches. See Abstract
“We are proud of the work our funding has enabled and look forward to seeing further important discoveries that will improve the ability to diagnose, monitor and treat lupus and its manifestations.” noted Dr. Teodora Staeva, Chief Scientific Officer at the Lupus Research Alliance.