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Cleaved cell fragments possible MS marker

6/16/2015

A new study finds that B cells and the BCMA system constitute promising targets for the treatment of multiple sclerosis. Blocking their activity could inhibit the production of the autoimmune antibodies and lead to the development of optimized and personalized treatments.

Long-term antibody-mediated immunity is provided by so-called long-lived plasma cells. Researchers at Ludwig-Maximilians-Universitaet, in Munich, Germany, have identified a novel mechanism involved in regulating the lifespan of these antibody producing cells. This involves the shedding of a particular cell-surface receptor, named BCMA, which is known to bind factors that promote plasma-cell survival. As a so-called transmembrane receptor, BCMA extends through the cell membrane and projects into the extracellular medium. Gamma-secretase removes the exposed portion by cutting the protein inside of the plasma membrane. That this enzyme cleaves the receptor directly was a surprise. The cleaved fragment is stable, and can be detected in body fluids as soluble BCMA. Analysis of clinical samples from patients with multiple sclerosis have indicated that the molecule could provide a useful biomarker for the autoimmune disease, the authors say.

"In MS patients sBCMA levels were increased specifically in the cerebrospinal fluid, which bathes the brain and the spinal cord," says Meinl. "So, sBCMA is an indicator of the intensity of ongoing immune reactions. sBCMA is therefore well suited to serve as an informative clinical parameter for the assessment of the therapeutic effects of different treatment regimes on plasma cells."

Further clinical studies on agents that target BAFF and its receptors are currently underway.

The results were published in the online journal Nature Communications.



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