ARRA Investments in Autoimmune Diseases
Public Health Burden
Autoimmune diseases are a group of more than 80 chronic illnesses that develop when underlying defects in the immune system lead the body to attach its own organs, tissues, and cells. Although many of these are rare, they collectively affect 5-8 percent of the population, with a higher incidence reported in women. The causes of autoimmune diseases remain unknown, although genetic factors play major roles in susceptibility. Treatments are available for many of these diseases, but no cures have been discovered.
ARRA funded awards are supporting researchers whose studies are broadly applicable to many autoimmune diseases, as well as those studying specific autoimmune diseases. A number of awards are focused on understanding the basic biology of autoimmunity, improving detection and diagnosis, and developing more effective therapies. A few of these include:
Investigating the role of T cells in autoimmune diseases, by studying the role of a novel molecular mechanism underlying how a gene (
) maintains the function of regulatory T cells to suppress autoimmune diseases,
and how to induce this T cell response.
Establishing a mouse model to independently investigate the effects of genes and sex hormones on the development of autoimmune diseases. These studies will provide insight into why females are more prone to autoimmunity, as well as provide screening and treatment strategies for those with a predisposition to autoimmunity.
Conducting genetic studies on a cohort of 800 families in whom two or more members suffer from autoimmune disorders, in order to identify genetic risk factors for the development of autoimmunity.
Continuing development of a novel, low-cost approach for proteome-wide screening of sera from patients with specific autoimmune diseases; the goal of this work is to commercialize diagnostic assays for autoimmune diseases.
Establishing the Kaiser Permanente Autoimmune Disease Registry, a resource that will contain comprehensive clinical information and DNA for more than 26,000 patients with rheumatoid arthritis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis.
Type 1 Diabetes
Type 1 diabetes is a chronic disease in which a person’s immune system attacks the insulin-producing cells in the pancreas, such that they are unable to produce the insulin necessary to break down sugars in the blood. As a result, blood sugar levels remain high, leading to organ damage. ARRA funding for type 1 diabetes includes:
Collaborative work by a group of investigators pursuing three major projects: identifying markers of immune activity in type 1 diabetes; examining the interplay between genetics, environment, and the immune system in the pathogenesis of type 1 diabetes; and developing therapies for preventing and treating type 1 diabetes.
The development of a new technology to eliminate the T cells attacking the pancreas. This research will study two parallel approaches to selectively target these cells, which will provide a new level of efficiency in treating type 1 diabetes.
Multiple sclerosis (MS) is a disease in which the immune system attacks the central nervous system, leading to the breakdown of the myelin sheath surrounding the nerves. This results in loss of nerve function and disability. ARRA funding for MS includes:
Using a mouse model of MS to study the pathogenic mechanisms contributing to the destruction of myelin-producing cells.
Examining the mechanism of action of the FDA-approved drug Copaxone, used for the treatment of MS. Studies will dissect the early immunologic effects following start of treatment, and determine whether or not these are predictive of long-term immunologic and clinical benefit.
Inflammatory Bowel Diseases
Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn’s disease. Ulcerative colitis is a disease of the large intestine’s mucosal lining. Crohn’s disease, although generally confined to the small intestine, can affect the entire digestive tract, and can penetrate deeper into the intestinal wall. Both are caused by a misregulated immune response leading to uncontrolled inflammation. ARRA funding for IBD includes:
Developing a novel high-resolution side-viewing colonoscope to allow visualization of the colonic mucosa at the cellular level, thereby improving detection and diagnosis of IBD.
Examining the regulatory mechanisms that control T cell function in the intestinal mucosa. Unbalanced T cell responses result in chronic inflammation. Regulation of this response is a therapeutic strategy for treating IBD.
Rheumatoid arthritis (RA) is a disease of the joints that occurs when immune cells attack the tissue lining the joints, leading to inflammation and damage. ARRA funding for RA includes:
Studying a newly discovered gene, B and T Lymphocyte Attenuator (BTLA), involved in the susceptibility of humans to RA. This work will provide a basic understanding of the disease.
Analyzing samples from an NIH-funded Phase II clinical trial to elucidate the mechanisms of tolerance induction in RA, in order to devise therapies for long-term disease control.
-- The Role of FoxP3 in the Regulatory T Cells -- Fang, Deyu (MO)
-- Regulatory T Cells in Autoimmune Disease -- Hafler, David (MA)
-- The Relative Role of Sex and Genes During Development of Systemic Autoimmunity -- Jorgensen, Trine (OH)
-- Mapping Autoimmune Phenotypes in Multiplex Families -- Gregersen, Peter (NY)
-- Novel Proteomic Arrays of In Vitro Expressed Proteins for Autoimmune Disease -- Lim, Mark (MA)
-- Kaiser Permanente Autoimmune Disease Registry -- Herrinton, Lisa (CA)
-- Immune Function and the Progression to Type 1 Diabetes -- Atkinson, Mark (AL)
-- Targeting CD8+ T Cell to Prevent B Cell Destruction -- Frelinger, Jeffrey (NC)
-- Autoimmune Encephalomyelitis and C-Rel -- Chen, Youhai (PA)
-- Role of T Cells in the Immune Modulation of MS -- Karandikar, Nitin (TX)
-- In Vivo Imaging of T-Cell Differentiation in Inflammatory Bowel Disease -- Yun, Seok (MA)
-- Regulation of Effector T Cell Function by Blimp-1 in a Murine Model of Colitis -- Martins, Gislaine (CA)
-- Analysis of Bidirectional Signaling Mechanisms for BTLA and HVEM in Autoimmunity -- Murphy, Kenneth (MO)
-- Immune Tolerance in the Therapy of Rheumatoid Arthritis -- Albani, Salvatore
Page Last Updated on June 30, 2018
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