Monday, 27 May 2013

T cell responses to VZV on fingolimod

Fingolimod reduce your T cell immune response to viruses. Is it important? #MSBlog #MSResearch

EpubRicklin et al. T-cell response against varicella-zoster virus in fingolimod-treated MS patients. Neurology. 2013 May 22.

OBJECTIVE: To study the immune response against varicella-zoster virus (VZV) in MSers before and during fingolimod therapy.

METHODS: The VZV-specific immune response was studied using interferon (IFN)-γ enzyme-linked immunosorbent spot assay, proliferation assays, and upregulation of T-cell activation markers in MSers before (n = 38) and after 3 months of fingolimod therapy (n = 34), in untreated (n = 33) and IFN-β-treated (n = 25) MSers, and in healthy controls (n = 22). Viral replication was analyzed by using real-time PCR in 76 peripheral blood mononuclear cell samples and 146 saliva samples.

RESULTS: Treatment with fingolimod led to a marked reduction of CD3+ T cells with a relative decrease of naive and central memory T cells and an increase of effector memory T cells. Expression of the activation markers CD137 and CD69 upon VZV stimulation was unaltered by fingolimod. However, the absolute number of cells proliferating upon VZV stimulation was reduced in the blood of MSers treated with fingolimod. Also, VZV-specific and Epstein-Barr virus (EBV)-specific IFN-γ-producing cells were reduced after fingolimod therapy. Seven of the 35 MSers treated with fingolimod showed signs of VZV or EBV reactivation in saliva compared with 3 of the 111 controls. None of the 76 tested samples showed signs of viral reactivation in the peripheral blood mononuclear cells.

CONCLUSION:  MSers treated with fingolimod show a slightly reduced antiviral T-cell response. This reduced response is accompanied by a subclinical reactivation of VZV or EBV in the saliva of 20% of MSers treated with fingolimod.

Varicella skin rash
Varicella penumonia

"What this study is testing is the ability of immune cells in the blood to respond to two herpes viruses, VZV (variella-zoster virus) and EBV (Epstein-Barr virus). VZV causes chicken pox and shingles and EBV infectious mononucleosis. There is little doubt that fingolimod reduces the ability of your T cells in the blood to respond to these viruses. This would partially explain the 3 deaths, that I am aware of in, in MSers on fingolimod due to herpses viruses; one case of herpes encephalitis and 2 cases of disseminated VZV."
"I am not sure if I wrote this paper that I would use the adjective 'slightly' to explain the reduction in antiviral T-cell responses due to fingolimod. It is as if the authors are wanting to play down their findings. Either fingolimod reduces or does not reduce anti-viral responses. This study shows it does. These results are not surprising as fingolimod is an immunosuppressive drug. What can be done about this reduction in anti-viral responses. All VZV negative MSers should have a VZV vaccine before starting fingolimod (this is part of our standard operating procedure) and MSers on fingolimod should be vigilant about infections. The latter is important as we have several antiviral drugs that work against some of the herpes viruses and if started quickly they should improve clinical outcomes."

"I must commend these investigators for doing this study; it is very important data that adds to our knowledge about fingolimod. I will also find it useful when counseling MSers about fingolimod."

CoI: multiple

1 comment:

  1. How does this fit in with the EBV/viral cause hypothesis?


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