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Director:
Yaakov Naparstek, M.D. Professor Medicine, Leiferman Chair
in Rheumatology
Background
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.
National Activities
- 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.
International Collaboration
- 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.
Organizational Structure
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.
Chairman: Prof. Yaakov
Naparstek, Chairman of Medicine, Hadassah University Hospital
Executive Board
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
Time table
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.
Yaakov Naparstek, M.D.
Professor and Chairman
Department of Medicine
Hadassah Medical Center
Jerusalem, POB 12000
Israel
Tel: 972 2 6777642
Fax: 972 2 6423216
E Mail: yakovn@cc.huji.ac.il
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