Involvement of CD 44 a molecule with thousand

Involvement of CD 44, “a molecule with thousand faces”, in autoimmune diseases Nathalie Assayag-Asherie, Itshak Golan, Lola Weiss, Lora Eshkar Sebban, Shimon Slavin, Itamar Raz and David Naor Supported by: D Cure Diabetes care in Israel and The Israel Academy of Sciences Israel Science Foundation

The inflammatory process

GENOMIC STRUCTURE OF THE CD 44 MOLECULE

In collaboration with Professor Yehiel Zick The Weizmann Institute

CD 44 FUNCTIONS * Cell-cell and cell-matrix interactions * Support of cell migration * Signal delivery for cell growth and cell differentiation * Transmission of apoptotic signals * Signal delivery for cell survival * Signal delivery for production of cytokines and chemokines * Presentation of chemokines and growth factors to cells with corresponding receptors * Docking of proteolytic enzymes on the cell surface and their presentation to relevant substrates * Internalization and degradation of hyaluronic acid

The inflammatory process

Anti-CD 44 m. Abs reduce pathological activities in the following experimental diseases: Name of disease Target CD 44 Reference epitope Malignant lymphoma in BALB/c mice Constant M. A. Zahalka, E. Okon, U. Gosslar, B. Holzmann, and D. Naor. J. Immunol. 154: 5345, 1995. Diabetes in NOD mice Constant L. Weiss, S. Slavin, S. Reich, P. Cohen, S. Shuster, R. Stern, E. Kaganovsky, E. Oken, A. M. Rubinstein, and D. Naor. PNAS 97: 285, 2000. Experimental allergic encephalomyelitis in (PLx. SJL) F 1 mice Constant S. Brocke, C. Piercy, L. Steinman, I. L. Weissman, and T. Veromaa. PNAS 96: 6896, 1999. Experimental colitis in BALB/c mice v 7 B. Witting, C. Schwärzler, N. Föhr, U. Günthert, and M. Zöller. J. Immunol. 161: 1069, 1998. Collagen-induced arthritis in DBA/1 mice Constant K. Mikecz, F. R. Brennan, J. H. Kim, and T. T. Glant. Nature Med. 1: 558, 1995; S. Nedvetzki, M. Walmsley, E. Alpert, R. O. Williams, and D. Naor. J. Autoimmunity 13: 39, 1999.

Dr Lola Weiss Department of Bone Marrow Transplantation and Cancer Research Laboratory, Hadassah University Hospital, Jerusalem, Israel

Nathalie Assayag Asherie The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel

Anti-CD 44 m. Ab reduces insulitis in NOD mice histopathological analysis PNAS, 97: 285, 2000

Dr Itshak Golan

GENOMIC STRUCTURE OF THE CD 44 MOLECULE

Sequence of V 4 -V 5 junction in CD 44 v 3 -v 10 of Keratinocytes in normal donors VARIANT EXON 4 ATG ACT G M T D VARIANT EXON 5 AT GTA GAC V D J. Clin. Invest. 111: 1211 -1220 (2003)

Binding of F 8: 33 Anti-CD 44 v. RA m. Ab to Synovial Fluid Cells of an RA Patient but not to his own PBLs

Question Is the binding of anti-CD 44 m. Ab to cell surface CD 44 delivers intracellular signaling leading to a functional outcome, such as apoptosis ?

Anti-CD 44 v. RA m. Ab +