Our Research

Autoimmune Disease

Autoimmune disease research

Autoimmunity, or autoimmune disease, arises from a dysregulation in the immune system such that it attacks our body’s own healthy organs and tissues. The immune system interacts with every organ system in the body so if it becomes dysregulated, autoimmune disease may also affect any organ. There are more than 80 different known autoimmune diseases. Many of these are treated with drugs intended to dampen the immune system’s response but, in many cases, the consequences of using these drugs on the overall immune system is poorly understood. 

Currently, we are studying the autoimmune diseases rheumatoid arthritis and inflammatory bowel disease.

Rheumatoid Arthritis

Rheumatoid arthritis, or RA, is a common autoimmune disease, affecting nearly one in every 100 Americans, and nearly three times as many women as men, according to the American College of Rheumatology. In autoimmune diseases, the body’s immune system attacks its own healthy tissue; in the case of rheumatoid arthritis, the immune cells attack the lining of the joints, causing painful swelling and even permanent deformities or disabilities in advanced stages.

NoneGary S. Firestein, M.D., working with his research team

Published data suggest that the initial steps of immune dysregulation that lead to rheumatoid arthritis begin years before the disease becomes clinically apparent. The immune mechanisms that ultimately lead to the development of active disease are poorly understood. Our research aims to pinpoint those mechanisms in the hopes of identifying drug targets for earlier treatment or even prevention.

Treatments initiated after permanent damage to bones and joints has begun can slow the accumulation of further damage and improve symptoms but are unlikely to reverse damage. Intervention before the damage occurs may be more effective at sustaining health and long-term functioning but without a better understanding of the immunologic mechanisms at play before the disease becomes clinically apparent, potential therapeutic targets are unknown. 

Together with researchers at the University of California San Diego and the University of Colorado Anschutz Medical Campus, we are deeply profiling the immune system in individuals with blood biomarkers that indicate they are at high risk of developing clinically active rheumatoid arthritis. By studying this cohort longitudinally, starting before and continuing after the individuals develop active disease, we hope to better understand the state of the immune system immediately before transition to clinical disease. In addition to important insights into the initiation of RA, this work could also inform our understanding of the development of other autoimmune diseases. 

Inflammatory bowel disease 

Inflammatory bowel disease, or IBD, is a class of autoimmune diseases that cause ongoing inflammation of the digestive tract and include the specific diseases termed Crohn’s disease and Ulcerative Colitis. Both conditions can cause severe diarrhea and abdominal pain and can be debilitating if severe. The exact cause of IBD is not clear but researchers believe the immune system mistakenly attacks the lining of the gut, triggering inflammation.

NoneE. John Wherry, Ph.D. working setting up an experiment

There is no cure for IBD; patients are typically treated with anti-inflammatory or immune-suppressive treatment, but these therapies don’t always work and, especially in the case of immune-suppression, can lead to other chronic health problems including higher risk of infection. Anti-inflammatory drugs that block the activity of an immune protein called Tumor Necrosis Factor-alpha (TNFa) are among the most effective therapies in patients with severe disease. Little is known however about the broader effects that this drug has on the immune system and why some patients don’t respond to this treatment. Together with researchers at the University of Pennsylvania, we are studying the effects of this potent anti-inflammatory on the immune system and trying to understand why it works in some patients but not in others. We believe that these studies will provide insight to new directions for novel treatments.