CD44 involvement in experimental collagen-induced arthritis (CIA)

CD44 is a pro-inflammatory cell surface molecule that supports cell migrati on and cell lodgment in target organs. Therefore, CD44 targeting with speci fic monoclonal antibodies (mAbs) should be useful for the inhibition of col lagen-induced arthritis (CIA) as well as other autoimmune diseases that are dependent on inflammatory cells. In the present paper, we confirm and expa nd previous reports showing the anti-arthritogenic effect of anti-CD44 mAbs directed against constant epitopes of the CD44 receptor. We demonstrate th at such anti-CD44 mAbs can induce resistance to CIA after disease onset. Ev en accelerated disease developed after two injections of type II collagen w as 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' frag ments partially inhibit CIA. This finding implies that the antibody blocks CD44 function rather than modulating CD44 cell surface expression or mediat ing Fc-dependent activities. Histopathological analysis revealed that the a nti-CD44 mAb markedly reduces the synovial inflammatory cellular response a nd the consequent damage to the joint. As CD44 is an alternatively spliced multistructural molecule, similar anti-arthritogenic effects may be achieve d by mAbs directed against CD44 isoforms expressed on the pathological cell s in question, but not on normal cells, thus leaving the physiological func tions intact. (C) 1999 Academic Press.