Relapsing Polychondritis Research
Jane Hoyt Buckner, M.D.
Autoimmunity is a deviation in the normal immune response. The individual’s immune system fails to recognize its own cells (“self-recognition”), which leads to inflammation and destruction of tissues. The immunologic events that lead to autoimmunity may occur at many levels: in the thymus gland (the area where self-recognition occurs), in the tissues of the body, or directly in the cells of the immune system. Dr. Buckner's laboratory is examining several aspects of the immune response to better understand the mechanisms leading to autoimmunity. Her laboratory has a particular interest in rheumatoid arthritis and relapsing polychondritis.
Dr. Buckner’s lab has three areas of focus:
1. To examine how different genes affect the self-recognition system.
2. To identify factors that determine how certain immune system cells respond in autoimmune diseases.
3. To examine the autoimmune response directed toward cartilage autoantigens in patients with relapsing polychondritis and rheumatoid arthritis.
Dr. Buckner's laboratory investigates the mechanisms underlying the immunologic recognition of self-proteins, and the immune deviation of this recognition that leads to autoimmunity.
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 that 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/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.
Who gets RP?
RP is an uncommon disease that affects approximately 3-5 individuals per million people. RP affects both men and women. It can affect individuals of all ages, it has been described in childhood and beginning as late as age 80, but most frequently occurs midlife.
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:
Other :
- Many other problems have been described in patients with RP.
- 30% of patients may suffer from another autoimmune disease.
Course of RP?
It was initially thought that all patients with RP would have severe health problems due to the disease. It is now known that there is a great deal of variation in the severity of the disease from person to person. Many individuals may have mild symptoms, which recur infrequently, while others may have persistent problems that become debilitating or life threatening. At this time it is not known how to predict how the disease will affect any specific individual.
How is RP treated?
Treatment for relapsing polychondritis is approached in a manner similar to other autoimmune diseases. A team approach is very helpful in treating this disease since it can involve many organs. Initial treatment usually includes prednisone and further medical treatment should be done with the supervision of a rheumatologist and may include other medications. Treatment of eye disease should be done in consultation with an ophthalmologist, and those individuals with respiratory symptoms may need to be followed by an otolaryngology or pulmonologist.
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 weekly 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.
Contact for this research study:
Pat Breen, RN
1-800-354-9527 x 67893
