Multiple Sclerosis Research Today is a free monthly online journal that collates and summarizes the latest research about Multiple Sclerosis, including details on diagnosis, symptoms, treatment, prognosis.

Anti-heat shock protein 90beta antibodies decrease pre-oligodendrocyte population in perinatal and adult cell cultures. Implications for remyelination in multiple sclerosis.

Cid C, Alvarez-Cermeño JC, Salinas M, Alcázar A

Depto. Investigacion, Hospital Ramon y Cajal, Madrid, Spain.

Lesions in the CNS of patients with multiple sclerosis (MS) often fail to remyelinate, resulting in neurological dysfunction. A key factor seems to be the inefficiency of oligodendrocyte precursor cells (OPCs). We recently reported antibodies against heat shock protein 90beta (Hsp90beta) in MS patients that recognized the antigen on the OPC surface. This study investigates the mechanism and result of anti-Hsp90beta antibody attack. These antibodies induced OPC death in culture in a complement-dependent fashion. Anti-Hsp90beta antibody-induced, complement-mediated OPC death only operated in these cells and caused a significant reduction in the number of O4-positive pro-oligodendrocytes (pre-oligodendrocytes). Adult cultured OPCs also expressed Hsp90beta on their cell surface and were attacked by anti-Hsp90beta antibodies leading to a significant decrease in the pre-oligodendrocyte population. In the presence of low levels of anti-Hsp90beta antibody--i.e. in the range seen in the CSF of MS patients--the complement concentration was critical to reduce the pre-oligodendrocyte population (via attack to OPCs). Higher concentrations of anti-Hsp90beta antibodies and complement became extinct the pre-oligodendrocytes. Complement 1-esterase inhibitor prevented these effects in the pre-oligodendrocyte population. These findings demonstrate, for the first time in vitro, a feasible mechanism to decrease the production of new oligodendrocytes, thus limiting the possibility of remyelination.

Published 29 September 2005 in J Neurochem, 95(2): 349-60.
Full-text of this article is available online (may require subscription).

© 2004-2008 Multiple Sclerosis Research Today. All Rights Reserved.