Antigen-Specific Adaptive Immune Responses in Fingolimod-Treated Multiple Sclerosis Patients
ABSTRACT T cells exit secondary lymphoid organs along a sphingosine1-phosphate (S1P) gradient and, accordingly, are reduced in blood upon fingolimod-mediated S1P-receptor (S1PR)-blockade. Serving as a model of adaptive immunity, we characterized cellular and humoral immune responses to influenza vaccine in fingolimod-treated patients with multiple sclerosis (MS) and in untreated healthy controls. Although the mode of action of fingolimod might predict reduced immunity, vaccine-triggered T cells accumulated normally in blood despite efficient S1PR-blockade. Concentrations of anti-influenza A/B immunoglobulin (Ig)M and IgG also increased similarly in both groups. These results indicate that fingolimod-treated individuals can mount vaccine-specific adaptive immune responses comparable to healthy controls.
SourceAvailable from: Matthias Mehling10/2014; 1(3):e28. DOI:10.1212/NXI.0000000000000028
[Show abstract] [Hide abstract]
ABSTRACT: Multiple sclerosis (MS) is an immune-mediated disease where T cells are thought to initiate an inflammatory reaction in the brain and spinal cord, resulting in demyelination and axonal pathology. Interfering with the activation and recruitment of immune cells reduces disease activity in MS. We review the mechanism of action and treatment effects of natalizumab and fingolimod, which interfere with the recruitment of pathogenic immune cells in MS. Fingolimod blocks the egress of activated lymphocytes from lymph nodes by binding to the sphingosine-1-phosphate (S1P) receptor 1, but may also have effects on S1P receptor-expressing cells within the central nervous system (CNS). Natalizumab reduces the migration of lymphocytes to the CNS by binding to the α4 integrin very late antigen 4. Fingolimod and natalizumab also have other effects, but these are less well understood. Both treatments are efficacious in reducing relapses, accumulation of persisting disability and magnetic resonance imaging disease activity. Both treatments are safe and well tolerated in the majority of patients, but due to a potential for serious side effects they are licensed as second line therapies or for treatment of highly active MS in most European countries. We conclude that fingolimod and natalizumab have well known effects on the migration of immune cells in MS and have substantial effects on disease activity in relapsing−remitting MS. Additional effects on disease progression, potential effects within the CNS and other effects on immune cells are still being clarified.European Journal of Neurology 01/2015; 22(3). DOI:10.1111/ene.12668 · 3.85 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The long term effects of fingolimod, an oral treatment for relapsing-remitting (RR) multiple sclerosis (MS), on blood circulating B and T cell subtypes in MS patients are not completely understood. This study describes for the first time the longitudinal effects of fingolimod treatment on B and T cell subtypes. Furthermore, expression of surface molecules involved in antigen presentation and costimulation during fingolimod treatment are assessed in MS patients in a 12 month follow-up study.PLoS ONE 10/2014; 9(10):e111115. DOI:10.1371/journal.pone.0111115 · 3.53 Impact Factor