CD44 involvement in experimental collagen-induced arthritis (CIA).
CD44 is a pro-inflammatory cell surface molecule that supports cell migration and cell lodgment in target organs. Therefore, CD44 targeting with specific monoclonal antibodies (mAbs) should be useful for the inhibition of collagen-induced arthritis (CIA) as well as other autoimmune diseases that are dependent on inflammatory cells. In the present paper, we confirm and expand previous reports showing the anti-arthritogenic effect of anti-CD44 mAbs directed against constant epitopes of the CD44 receptor. We demonstrate that such anti-CD44 mAbs can induce resistance to CIA after disease onset. Even accelerated disease developed after two injections of type II collagen was markedly inhibited by IM7.8.1 anti-CD44 mAb. Although KM81 anti-CD44 mAb is a less efficient anti-arthritogenic reagent than IM7.8.1, its Fab' fragments partially inhibit CIA. This finding implies that the antibody blocks CD44 function rather than modulating CD44 cell surface expression or mediating Fc-dependent activities. Histopathological analysis revealed that the anti-CD44 mAb markedly reduces the synovial inflammatory cellular response and the consequent damage to the joint. As CD44 is an alternatively spliced multistructural molecule, similar anti-arthritogenic effects may be achieved by mAbs directed against CD44 isoforms expressed on the pathological cells in question, but not on normal cells, thus leaving the physiological functions intact.
Nedvetzki
S
S
The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
Walmsley
M
M
Alpert
E
E
Williams
R O
RO
Feldmann
M
M
Naor
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001168:Arthritis / Q000209:etiology* / Q000276:immunology* / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology / Q000628:therapy; D002417:Cattle; D003094:Collagen / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes; D018960:Hyaluronan Receptors / Q000276:immunology*; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D020033:Protein Isoforms / Q000276:immunology; D051381:Rats
D000911:Antibodies, Monoclonal; D000939:Epitopes; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D003094:Collagen