Rheumatoid arthritis (RA) is a complex disease in which the patient’s immune system attacks its own tissue causing swelling and inflammation in the joints and damage of tissues and other organs. Much of the rheumatoid arthritis research being conducted focuses on immune mechanisms involved. Many of these mechanisms are shared with other autoimmune diseases that attack different organs, such as lupus (kidneys), multiple sclerosis (brain) and Type I diabetes (pancreas). The causes of rheumatoid arthritis are still unknown, but we do know that autoimmune diseases have a start and halt progression, with periods of active disease followed by periods of remission. Thus, thanks to the rheumatoid arthritis research discoveries of Gale “Morrie” Granger, PhD, the human immune system is the primary focus of research.
The human immune response consists of three different phases:
Current RA research grant recipients employ innovative approaches and modern technologies to identify, isolate and study the different phases of the immune response involved in rheumatoid arthritis. Scientists are looking at both the cellular and molecular level. We have hope that a new treatment for rheumatoid arthritis can be developed or better yet that a cure can be found.
Beatrice Bartok, MD, second-year grant recipient
University of California, San Diego
Dr. Bartok is studying joint tissues from human RA patients and mice. She has discovered how the normal joint cells become altered by the immune attack.
Damage in joints of patients with rheumatoid arthritis (RA) is induced by the patient’s immune system attacking its own joint tissues. However, a portion of this damage is caused by “resident” normal cells in the joint that have become altered during and after the immune attack. The altered resident cells undergo abnormal growth and healing which results in scarring, disfigurement and joint immobilization.
Potential: Dr. Bartok has discovered how the normal joint cells become altered by the immune attack. Her important findings can lead to the development of new drugs and treatments to block this destructive cellular response, thereby preventing and stopping the progressive destruction of joint tissues in RA patients.
Junxia Wang, MD, PhD, second-year ANRF grant recipient
Brigham & Women’s Hospital, a Harvard Medical School affiliate
Dr. Wang has identified the mechanism of how white blood cells called neutrophils leave the blood stream and migrate into joint tissues.
Neutrophils are white blood cells which are important for the body’s defense against infectious agents. However, these same cells enter the joint in rheumatoid arthritis in large numbers and over time cause swelling, pain and tissue damage.
Potential: The mechanism of the migration of neutrophils into joint tissues may lead to a therapy that will block the migration and subsequent damage to joint tissues. These results can lead to new methods to prevent the onset and control tissue damage in RA and other forms of inflammatory arthritis by blocking the migration of neutrophils into the joint.
George Kalliolias, MD, PhD, second-year grant recipient
Hospital for Special Surgery
New York, NY,
Dr. Kalliolias uses novel technologies to characterize and understand the role of synovial fibroblasts, resident joint cells that become activated in rheumatoid arthritis, as potential targets for new treatments.
None of the existing therapies for RA targets these cells. Dr. Kalliolias’ studies have shown that synovial fibroblasts display an uncontrolled inflammatory response to factors found in abundance within the inflamed joint of RA patients. These findings led to the hypothesis that these cells in the RA joint lack the appropriate “brakes” that should turn off inflammatory responses.
Potential: Dr. Kalliolias is testing this hypothesis to identify strategies to terminate or block the production of inflammatory and tissue destructive mediators by synovial fibroblasts which he hopes will lead to a new therapy targeting these cells.
These studies seek to understand and perhaps stop the immune response at its inception.
Expansion Phase studies
In patients with rheumatoid arthritis, once the initial immune cells identify the patient’s own tissues as “foreign”, they undergo a period of rapid cell division, or “expansion.” In the effort to find what causes rheumatoid arthritis, scientists have identified that specific cells and multiple cytokines may be involved in this complex process.
Invasion and Tissue Destructive Phase
In this third phase of the immune response, investigation into processes that cause tissue damage is directed at developing treatment for rheumatoid arthritis. Focusing on alleviating symptoms and stopping the damage from progressing.