Saturday, 11 June 2016

How does beta interferon work

Rizzo F, Giacomini E, Mechelli R, Buscarinu MC, Salvetti M, Severa M, Coccia EM.Interferon-β therapy specifically reduces pathogenic memory B cells in Multiple Sclerosis patients by inducing a FAS-mediated apoptosis. Immunol Cell Biol. 2016. doi: 10.1038/icb.2016.55. [Epub ahead of print]
Growing evidences put B lymphocytes on a central stage in Multiple sclerosis (MS) immunopathology. While investigating the effects of Interferon (IFN)-β therapy, one of the most used first-line disease-modifying drugs for the treatment of Relapsing-Remitting MS (RRMS), in circulating B cell subpopulations we found a specific and dramatic decrease of CD27+ memory B cells. Interestingly, memory B cells are considered a population with a great disease-driving relevance in MS and resulted to be also target of B cell depleting therapies. In addition, Epstein-barr virus (EBV), associated to MS aetiopathogenesis, harbors in this cell type and an IFN-β-induced reduction of the memory B cell compartment, in turn, resulted in a decreased expression of the EBV gene Latent membrane protein 2A in treated patients. We found that in vivo IFN-β therapy specifically and highly induced apoptosis in memory B cells, in accordance with a strong increase of the apoptotic markers Annexin-V and active Caspase-3, via a mechanism requiring the FAS-Receptor/TACI signaling. Thus, efficacy of IFN-β therapy in MS may rely not only on its recognized anti-inflammatory activies but also on the specific depletion of memory B cells, considered to be a pathogenic cell subset, reducing their inflammatory impact in target organs.

How does beta interferon work, we are not sure but it inhibits genes that affect viral replication  and these interfere with normal cell function and can induce blocking cell replication. B cells replicate very fast. In the era that B cells need to be targeted this study reports that there is a decrease in CD27+ B cells. Is this why it works. However we know that it does not work as well as alemtuzumab or ocrelizumab. 

5 comments:

  1. So many unknowns in MS - what starts the disease, why it perpetuates, what the disease process is, particularly in progressive MS. And we don't know how one of the oldest DMTs works. There's still nothing dramatic for progressive MS, nothing for whatever it is that triggers the disease, the damaging immune response. Nothing effective without potentially very serious side effects.

    I've just depressed myself.

    I'm going to nurse my Himalayan blue poppy seedlings. At least they are looking healthy and hopeful.

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  2. But why beta interferons have so low efficiency if they act in replication pathway of B cells?
    That's what I'm wondering ...

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  3. How was beta interferon discovered? Why did someone think 'oh this might work?'

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    1. It is anti-viral MS is caused by a virus so we throw in alpha interferon trial failed gamma interferon made mS worse and beta interferon lucked out

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  4. Simple fact of the matter is that is that B-interferon does not work in preventing progression in MS. It reduces relapses above placebo by 30%, reduces MRI activity but has zero effect of disease progression. So why is anyone studying how it works? Probably to cash in for stockholders by claiming relevance in the "B-cell era" of MS.

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