The National SLE (Lupus) Center
Systemic lupus erythematosus (SLE) is a common chronic rheumatic disease that usually affects young women, and is associated with wide-ranging clinical manifestations.
The etiology of lupus is not well understood. It is thought to result from a disorder in immune regulation system whereby an immune response is induced against host antigens and subsequently leads to inflammation and irreversible damage to target organs. It usually pursues a chronic course and may lead to death due to lesions affecting the kidneys, the central nervous system and other vital organs.
The current therapy of lupus is based on corticosteroids and cytotoxic agents, which suppress the over-reactive immune system. This therapy, however, is not specific and its inevitable side effects may themselves be fatal.
Although the disease is known for many years, and its serological markers have been defined, there has been no major breakthrough in the understanding of lupus and in the treatment of this disease in the last two decades, and SLE still leads to severe morbidity and mortality in its victims- mainly young women. There are a variety of reasons for our failure in the understanding and treatment of this incapacitating disease:
1. Clinical heterogeneity.
One difficulty in the study of lupus lies in its complex clinical course and clinical heterogeneity. SLE crosses the different medical specialties, such as rheumatology, endocrinology, neurology, cardiology, gastroenterology, and dermatology, and because such specialties usually focus on singular diseases within their particular category, it has been difficult to combine efforts and to focus on the whole clinical picture of this disease.
2. The misconception of SLE as a rare disease.
The interest of the major funding agencies and the pharmaceutical companies in SLE did not represent the scope of this disease. Until recently, SLE has been faultily believed to be a rare disease. This is definitely a misconception. More than 16,000 Americans develop lupus each year. It is estimated that 500,000 to 1.5 million Americans have been diagnosed with lupus. SLE is the third most frequent autoimmune disease after Diabetes and Rheumatoid Arthritis, and is more common than Multiple Sclerosis which has received a lot more attention due to strong and effective lobbying. Part of this underestimation of the disease may be due to the "gender factor".
3. The "gender factor".
Another possible cause for the relative lack of progress in the deciphering of lupus may be in the gender attitude. Lupus is a women's disease. More than 90% of its victims are young women, and, even though there is some universally accepted knowledge about SLE, its victims--mainly women--have suffered from this lack of focus and scattered research approach.
Getting a proper diagnosis is sometimes as difficult as living with the disease itself. Victims face problems not only because physicians don't always think of SLE, but also because of virtually who they are, namely, women in the childbearing years. As a rule, this is a time in a woman's life when she looks healthy, and looks can be deceiving. Often, women who suffer from autoimmune diseases like SLE are not taken seriously when they first begin consulting their doctors. The symptoms are likely to be vague in the beginning, with a tendency to come and go, and hard to describe accurately to her physician. In a typical scenario, she is then shunted from specialist to specialist and forced to undergo a battery of tests and procedures before a correct diagnosis is made, which can sometimes take years.
A survey by the American Autoimmune Related Diseases Association, Inc. (AARDA) has shown that over 65 percent of patients with autoimmune diseases in general have been labeled hypochondriacs or chronic complainers in the earliest stages of their illness. This can be devastating to a young woman who may then begin to question her sanity as she tries desperately to find out what is wrong. Tragically, many of these patients suffer significant damage to their organs in the meantime and end up carrying this health burden with them for the rest of their lives because of the delay in diagnosis
The Need for a National Center
In Israel there are at least 5000 SLE patients, most of whom are treated in the major hospitals' rheumatology and clinical immunology centers. Due to the variability of symptoms and clinical course of the disease, up until now there was no one center with a sufficient number of patients presenting a specific range of symptoms that will enable a good documentation of the clinical course of the disease. Similarly, there was no single center that would be able by itself to address the complicated clinical questions that remained unanswered in this disease.
In recent years, extensive clinical and research activities are being conducted in research centers in Israel to better understand the etiology of the disease and to develop more specific therapeutic modalities. Israeli scientists have acquired an international reputation in the field of SLE.
There is definitely a growing interest among Israeli SLE specialists to join efforts in the deciphering of this complicated and devastating disease. Forming a national consortium and a national registry will enable us to answer specific questions that can not be answered by the separate centers. This registry includes the clinical data of the patients, their family history, as well as a bank of serum and DNA samples.
Such a clinical registry enables us to document the clinical course of SLE in the different ethnic populations in Israel and serves as a basic resource for clinical trials to defined SLE problems. The DNA and serum bank together with the clinical registry enables us to use the genetic material for DNA analysis and for genotype-phenotype analysis. In this era of the human genome project, such a "DNA bank" from relatively closed populations (Ashkenazi Jews, Sephardic Jews, Arabs, etc.) can serve in the near future as a unique tool for the deciphering of lupus-associated genes. This gene-bank will be available to the international community, for research of lupus related genes of interest
In order to improve the medical care of lupus patients and extend the basic and clinical research, we felt it was valuable to establish a national center for the study of lupus that would centralize and coordinate all these activities.
The aims of the center are:
- To form a national clinical consortium of the centers and physicians that treat SLE patients in order to form a national registry and define clinical guidelines.
- To build an SLE serum and DNA bank.
- To construct national clinical protocols that will answer critical questions in the treatment of SLE.
- To support research directed at the treatment of SLE in Israel.
- To enhance international collaborations.
- Create a national SLE registry including clinical data and blood and DNA samples of SLE patients. The registry will be used for further serological and genetic analysis as well as national clinical trials.
- Form a national consortium of the centers that treat SLE patients in order to form national clinical guidelines, and to answer controversial questions regarding the treatment of SLE. (i.e. Prolonged immunosuppression versus more specific immunotherapy. Methods to reduce effect of treatment on fertility etc.). The Clinical SLE Consortium will decide on the priority of the questions to be addressed, and will form the protocols of the trials and help in performing the trials.
- Form the basis for the clinical evaluation of new therapeutic modalities that are being developed in Israel.
- Support young Israeli researchers who are studying SLE, in their first steps of research.
The center has two organizational bodies. One- the executive board that will decide on the funding of the projects, and the other-the clinical consortium that will combine the representatives of the centers that will participate in the registry and the trials. The executive board will be a permanent body. The clinical consortium, on the other hand, may expand and include more centers that treat a significant number of SLE patients. It is indeed one of our aims to include in the clinical consortium all the clinical lupus centers in Israel.
Prof. Yaakov Naparstek
- The Center will organize international workshops that will deal with the major questions regarding the treatment of SLE. These workshops will attempt to define the major questions and major directions of research to be dealt with in the near future in Israel and abroad, and will form the basis for international collaborations. An example of such a workshop was the international workshop on Anti-DNA antibodies organized in Jerusalem in 1999 by Prof. Naparstek and Prof. Eilat and supported by the National Academy of Sciences and the Lupus foundation of New York.
- Form a fund that will make it possible to send Israeli physicians and researchers to learn new technology that will assist in the promotion of the treatment of SLE.
- Make the Israeli Gene-Bank available to researchers and international centers that are studying the genetics of SLE.
Prof. Irun Cohen, Department of Immunology, Weizmann Institute of Science
Prof. Alan Rubinow, Head, Rheumatology Division, Hadassah Medical Center
Prof. Yehuda Shoenfeld, Head, Department of Medicine, Sheba Medical Center, Tel- Hashomer
Members of the clinical consortium
Prof. Mahmud Abu-Shakra, Soroka Hospital, Beer-Sheva
Prof.. Dan Caspi, Tel-Aviv Sourasky Medical Center, Tel-Aviv.
Dr. Margalit Lorber, Rambam Hospital, Haifa
Prof. Yaakov Naparstek, Hadassah University Hospital, Jerusalem.
Prof. Yehuda Shoenfeld-Sheba Medical Center, Tel-Hashomer
During the first year, we are concentrating on setting up the methods and building the infrastructure for the data and sample banks and start with the collection of the clinical data, and the serum and DNA samples. We will plan and choose the clinical trials to be performed in the next two years.
In the second and third year we will continue with the data and sample collection and start one or two trials.