Registry and Repository
In order to develop a comprehensive understanding of relapsing polychondritis we have established the RP Registry. This registry has been developed in order to assemble accurate clinical information including: disease presentation, disease manifestations, co-morbid diseases, family history, exposures and treatment responses. This information is updated on an annual basis in order to develop an understanding of the course of disease, and response to therapies in patients with RP. The sample repository includes DNA, serum, plasma and PBMC that can be used for studies of the underlying pathogenesis of RP, as well as to develop test for diagnostic and prognostic purposes. Together this information will allow us to better understand the variety of clinical problems that face patients with RP, and identify whether there are factors that predict the severity of disease, and develop an understanding of how this disease differs among individuals with RP. The ability to match clinical information with laboratory findings will allow us to make connections between findings that predict disease activity, severity and outcome, all of which will have the potential to aid in the care of patients with RP in the future.

T cell responses to cartilage derived antigens
T cells control and direct the immune system. In the normally functioning immune system these cells fight infections and control tumors. However, these same cells are implicated in the development of autoimmune diseases. The presence of CD4 T cells at the site of inflammation in RP suggests that they may be targeting the cartilage, leading to inflammation and destruction of these tissues. Our laboratory has attempted to identify the protein that is the target of the CD4 T cells in RP, and to isolate these T cells for further study. We have found that the majority of patients with RP have T cells which are activated by cartilage, specifically type II collagen. We have also been able to isolate and study these T cells in the laboratory. Our present studies continue to expand on this work, by examining more individuals for these collagen specific T cells and by searching for other cartilage proteins that may be the target of the immune system in RP.

Antibody response in RP
Antibodies are proteins made by the body which can identify and bind to foreign proteins. Antibody responses created by vaccines or past infections protect us from future infections. However, in many autoimmune diseases antibodies that are directed against proteins in the body are present, and sometimes cause disease. In the past it has been shown that 50-70% of patients with RP make antibodies against type II collagen, the main component of cartilage. We are studying these antibodies in RP patients to identify whether they are present, if these antibodies can be used to aid in diagnosis, and whether these antibodies cause disease.
Recently, we have identified antibodies against another component of cartilage, matrilin, and we are extending that work to other proteins as well. Identifying additional antibodies may explain the source of inflammation in RP. Identifying a panel of autoantibodies specific to RP will aid in diagnosis and prognosis for patients and the physicians treating them.

Genetics and RP
Predisposition to many autoimmune diseases has been demonstrated to have a genetic component involving the HLA genes. The Virginia Mason Research Center is well known for its work in understanding how HLA genes contribute to rheumatoid arthritis, juvenile rheumatoid arthritis and diabetes. Therefore it is natural for us to look at the influence of the HLA genes in RP. The HLA genes are a large family of genes that are important in the function of T cells. These genes can be examined to see if a specific gene is found more frequently in individuals who suffer from a disease. While these genes themselves can be found in a person without disease as well, we think of them as predisposing to, but not causing disease. In order to identify genes that may play a role in a disease a large number of individuals must be studied. Such studies are now underway in our laboratory.

What is RP?
What is Relapsing Polychondritis?
Relapsing Polychondritis is a disease that causes inflammation of cartilage. It can affect many parts of the body but the cartilage that is most frequently involved in this disease is that found in the outer ear, the bridge of the nose and the trachea. The inflammation in these areas is episodic and leads to redness and pain in the affected areas, and can later lead to loss of cartilage.

How is Relapsing Polychondritis diagnosed?
The diagnosis of Relapsing Polychondritis is based on a series of clinical criteria, which include episodes of inflammation involving cartilage structures. The diagnosis can be further confirmed by taking a biopsy of the affected cartilage for pathologic examination. No blood test has yet been developed that is diagnostic for RP.

What causes RP?
It is not known what causes this disease. But it is thought to be an autoimmune disease. This means that it is caused by the immune system attacking the body, and causing inflammation and tissue destruction.
What happens to patients with RP?
Patients with RP may have some of the problems below:
· Inflammation of cartilage:
· The ears and/or the nose may become swollen, red, warm and tender. The throat may become tender or the voice hoarse.
· Destruction and thickening of cartilage:
· Collapse or thickening of the outer ears
· Collapse of the bridge of the nose referred to as a saddlenose
· Difficulty breathing due to thickening or the collapse of the trachea
· Arthritis
· Pain and swelling of the joints
· Rib pain (costrochondritis)
· Hearing and Balance Problems Eye inflammation:
· Red, painful and swollen eyes due to one of the following uveitis, iritis, scleritis, episceritis, conjunctivitis.
· Vasculitis:
· Involvement with large vessels particularly the ascending aorta.
· Rashes or organ specific problems
· Renal Involvement
· Glomerulonephritis
· Other
· Many other problems have been described in patients with RP.
· 30% of patients may suffer from another autoimmune disease.

Research being done on RP:
Although RP is rare, medical research is being done to try to expand our understanding of the disease. Physicians continue to observe patients and their response to different treatments, and report their findings in the medical literature. Several groups of scientists are examining animal models of the disease, and others are trying to identify new laboratory markers of disease activity.
The ideal approach to understanding an uncommon disease is to gather information from as many patients as possible. Dr. Jane Hoyt Buckner, M.D. has been studying RP since 1996 and has established a RP registry and sample repository. Her work is designed to examine both the clinical and immunologic questions important to understanding RP. Presently her work includes establishing a database of information on patients with RP, so that the number individuals affected and the course of disease can be better documented. Dr. Buckner is also using blood samples donated by patients for her studies in order to expand our understanding of what is causing relapsing polychondritis. These studies include studies of the genes that may contribute to disease, the antibodies that patients make against collagen and the T cells which may be driving the inflammation of cartilage. The goal of this work is to better be able to identify patients with relapsing polychondritis by developing better laboratory tests, to be able to better predict the potential disease activity in patients and to develop improved therapies and potentially a cure for patients with RP.

Relapsing Polychondritis Clinic at Virginia Mason Clinic
· Dr. Buckner has a monthly clinic devoted to seeing patients with relapsing polychondritis.
· When possible it is helpful to have a referral from your physician, and to bring your medical records at the time of your appointment.
· Visits to this clinic are considered medical consultations, and patients seen in the RP clinic will be billed for the visit unless they make specific arrangements with Dr. Buckner prior to their visit.
· An appointment can be made by calling (206) 223-6824

How you can participate in this research
Any individual with relapsing polychondritis is welcome to take part in Dr. Buckner's research. There are several ways in which people may participate.
· Become part of the RP Registry- We have established the registry, which allows us to gather information from people with RP. To participate we ask that you fill out a form about yourself and your illness. Once we receive that information we will then contact you to verify that information for our database. We will then contact you on an annual basis to gather up to date information on what has happened to you in the past year. All information is confidential.
· Donate a blood sample for the RP sample repository. Blood samples can be drawn by your local laboratory and sent to our laboratory via federal express. We supply the necessary kits for this process. These samples are used for studies of the immune response in relapsing polychondritis, and to evaluate potential genes involved in the disease. These are research studies, and although we hope to develop useful lab tests for clinical use in the future, these tests are not used in the management of individual patients.

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