Introduction
Relapsing polychondritis (RPC) is an uncommon disease with an estimated incidence of 3.5 cases/million. The disease has been described in individuals ranging from childhood to 90 years of age but occurs most frequently between the ages of 40 and 60. The hallmark of RP is chondritis (inflammation of cartilage) involving the ear, nose and trachea. Inflammation at these sites can lead to cartilage destruction and result in deformity of the ears and the nose, and obstruction of the trachea which leads to difficulty breathing. Other inflammatory problems are seen in RP including: arthritis, eye inflammation, hearing and balance disturbances, vasculitis, and rarely kidney or brain involvement. In addition, up to 30% of patients with the diagnosis of RP have another autoimmune disease. RP is a disease that affects each individual differently, and may be mild or very severe. The diagnosis of the disease by a physician is based on a set of clinical criteria, determined by the patient's history, physical exam and when possible a biopsy of the affected cartilage. There is no specific blood test for the disease. Treatment is based on our understanding of other autoimmune diseases, and includes use of NSAID's, prednisone and immunosuppressive drugs.The cause of RP is still unknown, but there are several lines of evidence that suggest that an autoimmune response directed against cartilage may lead to this disease. This evidence includes: the presence of both T cells and antibodies at the sites of inflamed cartilage, the presence of antibodies directed against cartilage in the blood of patients with RP, animal models of RP, and the clinical observation that immunosuppressive medications can uccessfully treat some patients with RP.
RP is a disease for which there are many unanswered questions and problems. The central questions that we focus our research on are: "What is the cause of RP?" and "How does the immune system contribute to this disease?". To answer these questions we are examining the immune system's response to cartilage in this disease. But our work touches on more practical problems as well including:
1) How to diagnose and follow disease activity in patients with RP, and
2) How to predict the disease course in each individual with RP.
We hope in the future to directly address the core question, "How best to treat patients with RP?"
Research Program in RP
Understanding the cause of an autoimmune disease has many facets: identifying the part of the immune system which is attacking the body's tissues, then identifying the target of the abnormal immune response, and identifying any genes which lead to disease. In RP there is evidence that both the humoral (antibody) and cellular (T cell) arms of the immune system are involved in the disease. Blood samples from individuals with RP allow us to test whether antibodies directed against cartilage or T cells activated by cartilage are present in RP. Our work to date has demonstrated that both antibodies and T cells directed against cartilage are present in some patients. We have taken the next step, identification of the component of cartilage causing the immune response. One such component is type II collagen, the main protein in all cartilage. We have found that over 50% of patients make antibodies, and 40 to 50% of the patients have T cells reactive to type II collagen. We have also identified a new cartilage protein, matrilin-1, which causes an autoimmune response in some patients. Intriguingly, this protein is only found in the cartilage of the ear, nose and trachea, the sites of most inflammation in RP. There are many component parts of cartilage, and we plan to continue searching for other proteins that are targets for autoimmunity in RP.
Our ability to identify antibodies and T cell responses to type II collagen, has further allowed us to study in fine detail the character of the immune response to this protein in RP patients. These details may allow us to understand the underlying problem with the immune system in RP, and what drives it. Fortunately, we have been able to follow the immune response to cartilage in some patients over several years, and we have noted changes in the immune response to these individuals over that period. We hope that these changes may give us clues to what may cause progression or remission of disease. The practical application of these findings include the development of new diagnostic tests, the ability to follow disease activity and potentially predict disease flares, and identify the best forms of immunotherapy.
Genes are known to play a role in many autoimmune diseases, particularly in predisposing individuals to development of disease. The HLA family of genes has been shown to predispose to diseases such as rheumatoid arthritis, systemic lupus, multiple sclerosis and juvenile diabetes. We are examining the role these genes play in RP at this time, and in the future we will be able to look at other genes that play a role in autoimmunity.
In order to do this work we must acquire blood samples from individuals with RP. We have been very fortunate to have a large number of individuals throughout the United States participate in this work. We hope to expand the number of RP patients participating in the near future. With a large group of participants we are able to make much more headway into understanding this disease. Since each patient can be affected in different ways; severity of disease, the site of inflammation, and disease activity at the time that we receive their sample, we also need detailed information about each participant. To aid us in this work we have now established a database with which to keep all of the clinical and laboratory information on patients. This has been done to improve our ability to examine and interpret data, and also to assure confidentiality for each participant.
Future Plans
We began our research in RP in 1997 with the goal of examining the immune response to cartilage in individuals with RP. Due to the large group of RP patients participating in this work and the financial support from individual donors and the Arthritis Foundation we plan to expand our RP research program. We will continue to address the immunologic mechanism and genetic contributions in RP, with hopes of understanding the underlying disease process. Further, we hope to use this information to develop tests for diagnosis and prediction of disease activity. We also plan to expand our clinical database in order to better predict what patients with RP can expect in terms of their long term health and to identify the role that factors such as previous illnesses, exposures, or family history play in disease development.
Support
This research is supported by a grant from The Arthritis Foundation and by The Virginia Mason Relapsing Polychondritis Research Fund, and The Constance Albrecht Research Endowment Fund.
Study Name: Etiology of Relapsing Polychondritis and Autoimmune Diseases
Category: Arthritis
Currently accepting participants? Yes - please read the description below and contact the study coordinator if you are interested.
Study Coordinator: Kelly Yim
Phone: 206-223-6836 x 3
