The Lupus Research Alliance (LRA) held our annual scientific conference, the Forum for Discovery, online in true 2020 fashion. More than 150 funded investigators, scientific advisors, and partners from the pharmaceutical and biotech industries logged on from their computers around the world to hear about new discoveries from LRA-funded researchers.
LRA President Ken Farber emphasized that despite the challenges everyone has faced over the past year, the LRA is “keeping its eye on the ball” and focusing on supporting lupus researchers in their pursuit of better ways to prevent, diagnose, and treat lupus.
The scientific program featured an exciting keynote address from Mark M. Davis, PhD, Avery Family Professor of Immunology and Director of the Institute for Immunity, Transplantation and Infection at Stanford University. Dr. Davis—a member of the LRA Research Committee of the Board of Directors —described new results building on his paradigm-shifting findings published last year that transform our understanding of autoimmune diseases like lupus.
For decades, researchers have known about a process called “negative selection” that causes some T cells of the immune system to be destroyed in the thymus, a small organ that educates T cells and helps regulate the immune system. Negative selection is the body’s first defense against autoimmune disease. The thymus tests whether new T cells can recognize “self”—that is, proteins in a person’s own body. T cells that strongly recognize self-proteins, like a key recognizes a matching lock, are eliminated before they can attack the body. T cells that don’t recognize self-proteins, like a mismatched key, might be able to recognize a bacteria or virus, so those T cells are released from the thymus to join the immune system and patrol the body for infections. Yet a third type of T cells that mildly or moderately recognize self-proteins—like a key that fits in a lock but can’t quite turn it—escape negative selection and are also released from the thymus. When the immune system leaps into action to fight off a bacterial or viral infection, some of those mildly self-recognizing T cells get turned on and could potentially put a person at risk of developing autoimmunity.
Dr. Davis has identified a small subset of a distinct type of T cells, called Kir+CD8+ T cells, capable of suppressing the activity of the above-mentioned self-reactive CD4+ T cells. Thus, describing a mechanism that helps most people eliminate those potentially harmful, self-recognizing T cells before they can turn their attack from the infection to the body. While Dr. Davis originally identified these special suppressor CD8+ T cells in multiple sclerosis, he now demonstrates their presence at increased numbers in patient with lupus as well as in patients with COVID-19. Harnessing this mechanism of suppressing self-reactive CD4+ T cells arising in infectious disease may point to entirely new strategies to prevent and treat lupus and other autoimmune diseases.
Additionally, eight speakers shared their most recent discoveries from projects funded by the LRA. For example, Andrea Knight, MD, MSCE, a pediatric rheumatologist at the Hospital for Sick Kids, spoke about her work developing new tools to diagnose psychiatric disorders in individuals who developed lupus during childhood. By combining advanced brain imaging techniques, assessments of behavior, and analyses of proteins in the blood, Dr. Knight is creating an innovative “multi-level” profile to guide early detection and target treatment of these disorders in lupus.
Chandra Mohan, MD, PhD, University of Houston, described his research on ALCAM, a protein he discovered in urine of lupus patients with active lupus nephritis. This protein is a good predictor of long-term kidney outcomes for patients with lupus. Dr. Mohan and his team are now developing a test for urinary ALCAM that would allow the protein to be measured in a doctor’s office. Next, Dr. Mohan will test how ALCAM works in the kidney to see if it is also a good target for a potential treatment.
Another speaker, Jason Knight, MD, PhD, University of Michigan, shared new data on a protein in neutrophils that might be another target for lupus therapy. Neutrophils are cells of the immune system that are part of the defense against infections and may be involved in damaging the kidney, heart, and blood vessels in people with lupus. Several molecules that block the neutrophil protein are in clinical trials for other diseases, and Dr. Knight is studying if those molecules can protect against neutrophil damage in lupus models.
With these and other presentations, the 2020 Forum for Discovery highlighted the great strides made over the past year toward better understanding lupus and finding new targets for diagnosis and treatment. The new science described at the conference sparked lively discussion and exchange of ideas among attendees — a worthwhile opportunity for communication and collaboration during this socially distanced year. The LRA is grateful to everyone in the lupus community for maintaining momentum and the connection that propels discovery.
