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MULTICENTRE
STUDIES
THE ANTI-PHOSPHOLIPID TISSUE TARGETING IN APS: THE CNS AND
KIDNEY INVOLVEMENTS.
COORDINATORS
1Blank M, 2Meroni PL, 3Cervera R, 3Font J, 4Sloway
J. 5Jacobsen S and 16 Y Shoenfeld.
1The Center for Autoimmune Diseases,
Department of Medical 'B' , Sheba Medical Center, affiliated to Tel-Aviv
University, Israel, 2Allergy, Clinical Immunology and Rheumatology
Unit, IRCCS Istituto Auxologico, Department of Internal Medicine, University of
Milan, Italy. 3Department of Autoimmune Diseases, Institut Clinic
d'Infeccions i Immunologia, Hospital Clinic, Barcelona, Catalonia, Spain. 5Hvidovre Hospital, Hvidovre,
Denmark, 5The University of Chicago, Department of Medicine,
Chicago,IL, US, 6Incumbent of the Laura Schwarz-Kipp, Chair for
Research of Autoimmune Diseases, Tel-Aviv University.
PROJECT
During
the last years, several groups of clinicians and researchers proposed the
multisystemic involvement in APS associated not exclusively with coagulation
failure or recurrent fetal loss but with many diverse clinical manifestations
involving different organs (Lupus 12:497-8,2003).
These include neurological disorders, renal manifestations such as glomerular
calillary thrombosis or artery occlusions, cardiac and obstetric complications,
cutaneous features, skin nodules, adrenal findings ,
hepatic features and digestive system
involvement.
Employing tissue array, glycomics and proteomics approaches,
we found several novel autoantigens
which part of them entail
antibodies directed to:
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N-acetylgalactoseamine
(GalcNAc): These Abs were cross reactived with beta-2-glycoprotein-I (b2GPI).
Affinity purified anti-b2GPI, highly positive to GalcNAc and with specific
binding to neuronal cell line. The chorea antibodies, targeted the surface of
human neuronal cells, with specific induction of calcium/calmodulin-dependent
protein (CaM) kinase II activity.
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Transgelin
: One of the restricted proteins expressed exclusively in smooth muscle and
fibroblast cells SM-22-a. It is an actin-binding protein, 22-kD, which has a
role in actin polymerization. Recombinant transgelin (r.Trg) was expressed in a
bacterial system. Sera originated from patients with nephritis on APS
background, had elevated titers of anti-r.Trg antibodies. Immunization of naïve
mice with r.Transgelin induced glomerulonephritis. Anti-r.Trg bound kidney sections of APS patients with
nephritis. Preliminary data showed that
neutralization of transgelin may inhibit the actin-depolymerizing processes
leading to development of pathologic procedure.
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2) HSP-70kD protein : This heat shock protein
binds to nascent polypeptides to facilitate correct folding. The mechanisms by
which these proteins affect kidney and other organs in patients with APS
patients, are currently being deciphered.
Conclusion: Defining tissue specific target proteins, in correlation with clinical presentations in APS patients may have several advantages: 1) diagnostic and prediction for organ clinical features; 2) will be a future basis for developing therapy for systemic afflictions in APS patients.
For additional
information and applications, please e-mail: mblank@sheba.health.gov.il
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Last updated: 17 November 2005 |
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