More MS news articles for September 2002

The expression of apoptosis-regulatory proteins in B lymphocytes from patients with multiple sclerosis

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12225903&dopt=Abstract

J Neuroimmunol 2002 Sep;130(1-2):202
Seidi O, Sharief M.
Department of Neuroimmunology, Guy's, King's and St. Thomas' School of Medicine, Guy's Hospital, Hodgkin Building, SE1 9RT, England, London, UK

The pathogenesis of multiple sclerosis (MS) is thought to involve T- and B-lymphocyte-mediated autoimmunity.

However, the mechanisms that regulate lymphocyte activity in MS are poorly understood.

In normal circumstances, programmed cell death (apoptosis) contributes to the maintenance of lymphocytes homeostasis and the deletion of autoreactive cells.

Cellular commitment to apoptosis is partly regulated by the cell death receptor Fas, and the anti-apoptosis proteins Bcl-2 and FLIP.

Although there is emerging evidence that dysregulations of apoptotic pathways play a role in T-cell autoimmunity in MS, the expression of apoptosis-regulatory proteins in B cells from MS patients is largely unknown.

In this study, we analyzed the expression profiles of Fas, Bcl-2, and FLIP proteins in peripheral B lymphocytes from patients with relapsing-remitting and progressive MS, and from appropriate controls.

We observed a significant up-regulation of Bcl-2 and FLIP proteins in B cells from relapsing-remitting MS when compared to corresponding expression in progressive MS, or in noninflammatory neurologic controls and healthy individuals.

This cellular overexpression of Bcl-2 and FLIP proteins was not affected by treatment with interferon-beta, but was also observed in B cells from patients with systemic inflammatory diseases.

Our findings suggest that cellular overexpression of the apoptosis-inhibitory proteins in patients with relapsing MS may promote apoptotic resistance of potentially pathogenic, autoreactive B lymphocytes and consequently, may allow for continuing autoimmune tissue destruction.