Common Mechanisms of Autoimmunity
Novel Approaches for Therapeutic Insights
Breakthrough T1D (formerly JDRF), the Lupus Research Alliance, and the National Multiple Sclerosis Society have joined forces to identify common mechanisms of autoimmunity. These three leading autoimmune disease organizations are once again jointly funding research projects looking at common underlying disease mechanisms.
LEARN MORE
ABOUT THE GRANTS
Breakthrough T1D, the Lupus Research Alliance, and the National Multiple Sclerosis Society joined forces to accelerate research and discovery in autoimmunity and are proud to launch the 2025 Common Mechanisms in Autoimmunity grants.
Approximately 10% of the population has been diagnosed with an autoimmune disease (13% of women and 7% of men). While disease-specific research organizations study therapeutic strategies related to their autoimmune disease of interest (protection or elimination/blocking of target cell/tissue, stress responses, regenerative medicine), there are common approaches each is investigating to identify risk and rebalance the immune system in the context of autoimmunity:
- Genetic Susceptibility
- Autoantibody Activity
- Defective Negative Selection
- Enhanced Effector Activity
- Reduced Regulatory Capacity
- Inflammatory Signaling
- Environmental Triggers
25% of individuals with an autoimmune disease will likely develop a second autoimmune disease.
FULL GRANT DETAILS
Purpose
Breakthrough T1D, the Lupus Research Alliance, and the National Multiple Sclerosis Society will solicit grant proposals from investigators across autoimmune and other relevant fields to advance the understanding of autoimmunity and to obtain more specific insights into commonalities and differences of immune pathways that govern these disease processes.
The incomplete knowledge of immune networks, pathways, disease pathogenesis and heterogeneity across multiple autoimmune diseases remains a challenge towards achieving optimal therapies. This grant program invites innovative ideas that address needs across multiple autoimmune diseases in novel ways that may allow us to make faster progress together.
Objective
The overall objective of this program is to develop novel insight into the common mechanisms driving autoimmune diseases and accelerate the advancement of novel therapeutics strategies.
Scope
- Bring together investigators across autoimmune fields to advance the overall understanding of autoimmunity.
- Obtain more specific insights into commonalities and differences of immune pathways that govern disease processes.
- Fill gaps in the knowledge of immune networks, pathways, disease pathogenesis and heterogeneity across multiple autoimmune diseases to promote advancement towards achieving optimal therapies.
- Support the discovery and development of pan- or multi-autoimmune therapeutic strategies.
Projects selected for joint funding represent innovative ideas that address needs across multiple autoimmune diseases in novel ways that allow us to accelerate progress together.
Background
Autoimmune diseases are chronic disorders in which the immune system produces an inappropriate response against its own cells, tissues and/or organs that results in inflammation and damage. An incomplete knowledge of disease pathogenesis and heterogeneity among patients is very common in many autoimmune diseases, representing a real challenge that impacts the effectiveness of clinical trial design and the ability to predict whether a person will respond to a given treatment.
Grant Mechanism
Insight Award:
- 1-year pilot grant to investigate a mechanism underlying autoimmune disease, identify novel targets or mechanisms, or provide proof of concept for an innovative therapeutic strategy.
- Proposals considered must address a gap or need relevant to multiple autoimmune diseases and must be relevant toward at least two of the following:
- Multiple Sclerosis
- Systemic Lupus Erythematosus (or one of its manifestations)
- Type 1 Diabetes
- The goal of the Insight Award mechanism is to provide proof-of-concept data for novel insights into autoimmunity, and to serve as a vehicle by which to provide the rationale for assembling an Accelerator Award project team.
- First announcement of funding opportunity: Fall 2024
- Funding amount: Up to $150K (includes 10% indirect)
PAST AWARD RECIPIENTS
Breakthrough T1D-Lupus Research Alliance Co-Funded Research Awards
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.
Type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis share some—but not all—genetic risk factors, pointing to shared cellular mechanisms that cause disease. Dr. Cotsapas has developed a set of statistical tools to compare genetic information from these autoimmune diseases and identify the specific regions in the genome (DNA) affected across these diseases. He will use genome engineering—a way to make changes in the DNA—to create those exact changes in normal immune cells, to see how they affect the function of those cells. In this way, he will uncover the biological basis for risk shared across type 1 diabetes, lupus, and multiple sclerosis, and find specific pathways that can be targeted for drug development.
Thomas Pieber, M.D.
University of Graz, Austria
COMET common mechanisms in autoimmunity
Dr. Pieber and his team will apply highly sophisticated computerized machine-learning approaches on existing data from people with type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis and healthy volunteers, to identify the changes in different immune cells that are shared between the autoimmune diseases or unique to each. (Machine learning are computer programs that improve automatically through experience, which can help researchers find patterns from large-scale datasets.) This will generate a deeper understanding of commonalities and differences of immunological patterns in type 1 diabetes, lupus, multiple sclerosis, and rheumatoid arthritis, and will identify important pathways in immune cells that can then be tested for potential therapies.
3D and single-cell epigenome technologies for autoimmune disease
Dr. Satpathy will use the cutting-edge technology that can obtain genomic information on the status of each gene in an individual cell, allowing the detection of molecular differences that could be obscured in a pool of cells. Applying this approach on immune cells from healthy individuals and people with autoimmune diseases—including type 1 diabetes, systemic lupus erythematous, and multiple sclerosis—he aims to identify the genes and pathways associated uniquely with each disease and shared between the diseases. He anticipates that these studies will lead to a single-cell atlas of autoimmune disease-associated genetic factors, leading to novel insights into the shared and disease-specific mechanisms governing each disease and propose new strategies for therapeutic intervention.
Alexandra-Chloé Villani, Ph.D.
Assistant Professor Massachusetts General Hospital, Harvard Medical School
Single-cell genomics dissection of common immune networks driving autoimmunity
Dr. Villani will be leveraging the power of new state-of-the-art single-cell genomics and immunology technologies to identify the type and the characteristic of each single cell from blood and tissue samples from healthy individuals and people with lupus, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, as well as cancer patients treated with immunotherapy and, later, diagnosed with immune-related adverse events that mimic clinical features of autoimmune disease presentations. By comparing the composition of cell types and the states of the cells between tissues and blood specimens obtained from different diseases, she will be able to identify shared biological processes and pathways that could be targeted for therapeutic potential.
NR4A family as markers and mediators of B cell tolerance across autoimmune diseases: From antigen discovery to treatment
Julie Zikherman, M.D., Samuel Pleasure, M.D., Ph.D., Michael Wilson, M.D., Judith Ashouri, M.D., Joseph Derisi, Ph.D. (co-investigators)
University of California, San Francisco
When activated by infection or vaccination, B cells can produce antibodies against foreign invaders. “Self-reactive” B cells can produce autoantibodies, which can mistakenly tag cells in the body as foreign, thereby triggering the immune system to attack. Dr. Zikherman and colleagues previously showed that a small group of molecules—members of the NR4A family—are expressed at high levels in self-reactive B cells. She and her team of co-investigators will take advantage of high NR4A expression in self-reactive B cells to identify such cells in people with type 1 diabetes, multiple sclerosis, and systemic lupus erythematous. The investigative team will couple this with a novel high-throughput phage-display platform to screen samples from people in order to identify specific autoantigens and autoantibodies. The goal of this work is to define targets and genetic programs that guide disease-causing B cells to promote autoimmunity, to identify new disease biomarkers, and to develop new therapeutic approaches to eliminate such B cells selectively.
Breakthrough T1D-National MS Society Co-Funded Research Awards
Linking multiple disease compartments in T1D and multiple sclerosis
To date, no studies have been able to ‘connect the dots’ between more and less accessible immune compartments in type 1 diabetes and multiple sclerosis, mainly because of limited access to the more disease-relevant immune cells. In particular, it remains unclear how immune cells in the blood relate to those that are associated with the pancreas in T1D, or the central nervous system in multiple sclerosis. Dr. Bar-Or’s study will elucidate immune cell profiles in three distinct anatomic compartments: target organ-associated immune cells, tissue-draining (lymphatic) immune cells, and circulating blood. Through this, Dr. Bar-Or will learn not only about previously unexplored roles and relationships of immune cells in type 1 diabetes and multiple sclerosis, but also of similarities and differences that may exist between people with these two immune-mediated conditions. Ultimately, he hopes that he will identify measurements in the blood that better reflect what is actually happening in the tissue being injured, so he can more effectively and safely target them therapeutically and monitor response to therapies.
Analysis of antigen specific T cells in response to immune therapies in MS and T1D
In identical twins, one of whom has type 1 diabetes and the other who doesn’t, for example, both may have immune cells that are activated for beta cell molecules, but the immune cells in the unaffected sibling do not cause disease. Why? 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. In addition, anti-CD20 antibodies—against specific types of immune cells called B cells—have been used to treat both diseases, but the ways in which they change immune cells called T cells is not known. Dr. Herold will study how successful immune therapy changes these cells. He anticipates that it will lead to the identification of markers that can be used to track the diseases’ development, as well as suggesting combination therapies that may be used to extend the effectiveness of immune therapy.
Lupus Research Alliance-Funded Research Awards
Dissecting the genetics and host interactions of EBV-related autoimmunity
Epstein-Barr virus (EBV) is thought to be a possible trigger for many autoimmune diseases, in particular multiple sclerosis and systemic lupus erythematosus, but how EBV might promote these diseases is poorly understood. Dr. Robinson’s study will apply next-generation technologies to determine if and how EBV plays a central role in facilitating autoimmunity. He will investigate these key questions: Does EBV infection drive immune cell autoimmunity? How does EBV transform immune cells to promote autoimmunity in these diseases? Are there specific EBV strains that cause multiple sclerosis and/or lupus? Success of the study will identify the mechanisms by which EBV promotes multiple sclerosis and lupus and could lead to the development of next-generation therapies for these diseases.
ABOUT AUTOIMMUNE DISEASES
Autoimmune diseases are chronic disorders in which the immune system produces an inappropriate response against its own cells, tissues and/or organs that results in inflammation and damage. Approximately 24 million Americans suffer from the more than 80 autoimmune diseases. Some autoimmune diseases target one area of the body; for instance, type 1 diabetes (T1D) affects the pancreas while multiple sclerosis damages the nervous system. In contrast, systemic lupus erythematosus can affect the entire body, attacking virtually any organ or tissue.
Insufficient knowledge of how these diseases progress as well as their heterogeneity, that is, how the disease manifests differently in people—is a common challenge among type 1 diabetes (T1D), lupus and multiple sclerosis that this grant program aims to overcome. The 2024 awardees will examine possible common mechanisms that could cause or contribute to the development of at least two of the three autoimmune diseases. Ultimately, the goal is to find novel biological targets and strategies for therapeutic development to treat the diseases
About the Partnering Organizations
As the leading global type 1 diabetes research and advocacy organization, Breakthrough T1D helps make everyday life with type 1 diabetes better while driving toward cures. We do this by investing in the most promising research, advocating for progress by working with government to address issues that impact the T1D community, and helping educate and empower individuals facing this condition.
The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance’s Board of Directors fund all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. Visit LupusResearch.org to learn more about lupus and the research Lupus Research Alliance is funding to find new treatments and a cure.
The National MS Society, founded in 1946, is the global leader of a growing movement dedicated to creating a world free of MS. The Society funds cutting-edge research for a cure, drives change through advocacy and provides programs and services to help people affected by MS live their best lives. Connect to learn more and get involved: nationalMSsociety.org, Facebook, Twitter, Instagram, YouTube or 1-800-344-4867.