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Clinical
Activity
The Clinical Immunology and Allergy Unit is responsible for
the management of patients with autoimmune and allergic disorders,
as well as other pathological conditions of the immune system.
The senior physicians of the Unit, as well as the fellows,
take part in the treatment of in-patients, and the management
and follow-up of out-patients in the Unit's out-patient clinics
(allergy clinic, lupus and autoimmunity clinic, clinical immunology
clinic). The Unit is also responsible for service laboratories,
including the clinical immunology laboratory and the allergy
laboratory.
Research Activity:
The main research projects of the unit focus in autoimmunity,
SLE, autoimmune arthritis and the physiology of the allergic
response and include:
A. Role of protective antibodies
in autoimmune arthritis.
We have shown that resistance to autoimmune arthritis in the
rat Adjuvant Arthritis model is due to the presence of protective
antibodies. The target antigen for these antibodies has been
defined as a short peptide located on the surface of bacterial
65KD heat shock protein. The protective antibodies were able
to skew the cytokine network towards the non-inflammatory
cytokines. These findings can lead to a new therapeutic approach
for human Rheumatoid Arthritis.
B. The target antigen in SLE.
The target antigen for lupus antibodies has not been yet defined.
We have shown that a short peptide present in the C terminal
of laminin is the target for pathogenic SLE antibodies. This
has been shown in congenic, transgenic, SCID and lupus mice,
as well as in SLE patients. Inhibition of the interaction
of these antibodies with the laminin derived peptide suppressed
murine lupus kidney disease. The immunoadsorption of the human
pathogenic anti-peptide antibodies on a peptide bound sepharose
column was shown to delete the serum of the pathogenic antibodies.
This approach may lead to a novel and specific therapeutic
modality in the human disease.
C. Pathogenicity of lupus antibodies.
Anti-DNA antibody pathogenicity has been studied in a new
model of immunodeficient mice. The antibodies could be divided
into pathogenic and non-pathogenic subgroups. No genetic or
immunochemical differences were found between the two anti-DNA
subsets. However, they differed in their ability to cross-react
with the cytoskelletal protein a-actinin, that is known to
play a major role in the structural integrity of glomerular
filtration components. These results suggest that tissue injury
in SLE may be facilitated by molecular mimicry.
D. Tolerance Mechanisms in Lupus-Prone
Mice.
The integrity and breakdown of B cell tolerance in normal
and autoimmune mice has been studies in anti-DNA transgenic
mice, in which immunoglobulin heavy chain or heavy/light chain
combinations have been targeted to the proper chromosomal
sites of the mouse by homologous recombination in embryonic
stem cells. It was found that in normal mice, receptor editing
is the major mechanism of B cell tolerance, while clonal anergy
serves as a back-up tolerance mechanism. The maintenance and
collapse of these mechanisms in transgenic lupus-prone mice
are currently under investigation.
E. The pathogenesis of the allergic
response.
The physiology and differentiation of mast cells and eosinophils,
their response to repeated activation and their function and
cytokine production in normal individuals and in various diseases
and allergic conditions is studied.
F. The clinical course and epidemiology
of Latex allergy in hospital employees is analyzed.
Tel: (02) 6778028
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