Did you know that people with type 1 diabetes (T1D) are more likely to have a coexisting autoimmune disease? And someone with T1D is at a more than 3-fold increased risk of developing multiple sclerosis, as compared to someone who does not have type 1? And, if you have T1D and lupus, you are more likely to develop kidney complications, as opposed to people with just one disease.
That’s why Breakthrough T1D partnered with the Lupus Research Alliance and the National Multiple Sclerosis Society to advance the understanding of autoimmunity and to obtain more specific insights into commonalities and differences of immune pathways that govern these disease processes.
With the recent advances in immunology and the advent of innovative technologies, including advanced machine learning capabilities, autoimmune communities can now ask new questions or revisit old ones with new tools and for deeper, new insights.
“As far as technologies and methodologies go, we are in unprecedented times,” said Simi Ahmed, Ph.D., director of disease-modifying therapies at Breakthrough T1D and the architect behind this initiative. “The depth of information these tools can generate is remarkable and can shed light on key questions that remain unanswered for autoimmune diseases.”
“The best part is that three research organizations have joined forces to address knowledge gaps of mutual relevance for mutual benefit,” she adds. “This really is a fitting example of team science.”
The researchers will get a maximum of $450,000 for up to 2 years to generate the first tranche of results from their projects, which are outlined below.
Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling, to mobility challenges, blindness, and paralysis. An estimated 1 million people live with multiple sclerosis in the United States.
Lupus (systemic lupus erythematosus) is a debilitating condition in which the immune system mistakenly attacks the tissues in the body, such as your tendons, skin, internal organs, bones, and joints. An estimate suggests 322,000 Americans have definite or probable lupus.
Researchers Funded
Amit Bar-Or, M.D., University of Pennsylvania
Linking multiple disease compartments in T1D and multiple sclerosis
Dr. Bar-Or’s study will provide immune cell profiles in three distinct sites: target organ-associated immune cells, tissue-draining lymphatic immune cells, and circulating blood—the first to be able to do so—in type 1 diabetes and multiple sclerosis, with the goals of exploring hidden immune compartments, determining blood measures that better correspond with what is happening in the tissue being injured, and targeting them therapeutically.
Chris Cotsapas, Ph.D., Yale University
Identification of pathogenic pathways through genomic engineering to identify shared genetic effects on people with T1D, SLE, and MS
Dr. Cotsapas has developed a set of diagnostic tools to compare genetic information from different diseases and identify the regions in the genome (DNA) associated with the disease risks. He will use genome engineering—a way to make changes in the DNA—to determine the effect of a specific alteration of the DNA on the function of immune cells and uncover the biological basis for risk shared across autoimmune diseases, and find specific pathways that can be targeted for drug development.
Kevan Herold, M.D., Yale University
Analysis of antigen specific T cells in response to immune therapies in MS and T1D
Dr. Herold will study the immune cells that have been activated for target-organ molecules, in type 1 diabetes and multiple sclerosis, to identify features that account for their ability to cause autoimmunity, and will use anti-CD20 antibodies—an immunotherapy that targets immune cells called B cells—to find out how they change immune cells called T cells.
Thomas Pieber, M.D., University of Graz, Austria
COMET common mechanisms in autoimmunity
Dr. Pieber will apply advanced machine-learning approaches on existing data from people with type 1 diabetes, lupus, multiple sclerosis, and rheumatoid arthritis and healthy volunteers, to identify the shared or differential characteristics of their immune cells, which could uncover important pathways to be targeted for potential therapies.
William Robinson, M.D., Ph.D., Stanford University
Dissecting the genetics and host interactions of EBV-related autoimmunity
Dr. Robinson’s study will apply next-generation technologies to determine how Epstein-Barr virus (EBV) can trigger autoimmunity in multiple sclerosis and lupus. Understanding the mechanism underlying EBV’s role in autoimmunity could lead to the development of targeted therapies for these diseases.
Ansuman Satpathy, M.D., Ph.D., Stanford University
3D and single-cell epigenome technologies for autoimmune disease
Dr. Satpathy will use the latest technology that can obtain genomic information at a single cell level to identify the molecular pathways that cause autoimmune disease—including type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. He anticipates that these studies will provide novel insights into the shared and disease-specific mechanisms governing each disease that could lead to new therapeutic intervention.
Alexandra-Chloé Villani, Ph.D., Massachusetts General Hospital/Harvard Medical School
Single-cell genomics dissection of common immune networks driving autoimmunity
Using new state-of-the-art technologies called single-cell multi-omics, which combines the comprehensive nature of genomics with the microscopic resolution required to reveal distinct insights in the molecular make-up of every single cell comprised in tissues, Dr. Villani will compare the cell type and characteristic of each single cell from blood and tissue samples collected from healthy people and people with autoimmune diseases. Identifying the composition, state of the cells, and transcriptional programs making up the tissues and blood specimens obtained from different diseases will enable to pinpoint the biological processes and pathways shared between diseases that could be targeted for therapeutic potential.
Julie Zikherman, M.D. (with Samuel Pleasure, M.D., Ph.D., Michael Wilson, M.D., Judith Ashouri, M.D., Joseph Derisi, Ph.D., who will serve as co-investigators), University of California, San Francisco
NR4A family as markers and mediators of B cell tolerance across autoimmune diseases: From antigen discovery to treatment
Self-reactive B cells can produce autoantibodies that mistakenly tag the body’s own cells as foreign and trigger an attack by the immune system. Dr. Zikherman and co-investigators will take advantage of the unique expression of genes in the NR4A family to identify these cells, and will couple this approach with a novel high-throughput phage-display platform to identify autoantigens and autoantibodies in people with type 1 diabetes, multiple sclerosis, and lupus.
