Relapsing-remitting multiple sclerosis patients exhibit differential natural killer functional subpopulations.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) and has been known as T-cell mediated. However, the contribution of multiple cell types, notably natural killer (NK) cells, has also been reported. AIM: To quantify circulating total NK cells and its subpopulations, CD56 dim and bright, and to characterize the functional phenotype and IFN-γ and TNF-α production in relapsing-remitting patients treated with IFN-ß and in apparently healthy controls. RESULTS: CD56bright NK cells were found to be the least represented subpopulation. In relapse patients, the frequencies of IFN-γ-producing NK cells and their subpopulations were significantly decreased. In remission patients, CD56dim NK cells expressed high levels of HLA-DR and CD54. CONCLUSION: These results suggest that remission RRMS patients, although in an inactive stage of MS, present circulating NK cells with an activation phenotype, supporting the idea that NK cells may be relevant mediators in the MS pathophysiology.

Alterations in peripheral blood monocyte and dendritic cell subset homeostasis in relapsing-remitting multiple sclerosis patients.

Antigen-presenting cells participate and are implicated in the pathogenesis of multiple sclerosis. In our study we assessed the frequency of plasmacytoid (pDC) and myeloid (mDC) dendritic cells and the classical, intermediate and non-classical monocytes subsets, as well as their phenotypic and functional profile. We evaluated peripheral blood from relapsing-remitting patients treated with IFN-ß in remission and relapse phases and from healthy subjects. In remission, we observed a decrease of mDC/pDC ratio and a return to normal values in relapse. In both phases the frequency of non-classical monocytes decreases. Concerning the phenotypic characterization, an increased HLA-DR expression was observed in remission and a decrease in relapse, revealing alterations in monocytes and dendritic cells homeostasis.

Epitopes of HERV-Wenv induce antigen-specific humoral immunity in multiple sclerosis patients.

To verify the serological response mounted against antigenic peptides from HERV-Wenv protein, we analyzed 80 multiple sclerosis (MS) serum samples, 27 of which were re-analyzed after a 6-month follow-up IFN-ß therapy, and 73 healthy controls. Indirect ELISAs were carried out to detect antibodies specific for all the synthetic peptides derived from HERV-Wenv. Two antigenic peptides, HERV-Wenv93-108 (31.25%, p<0.0001) and HERV-Wenv248-262 (15%, p=0.02), were highly recognized by MS patients' antibodies when compared to healthy subjects. Moreover, antibody titer against these two peptides slightly decreased after six months of IFN-ß-based therapy.

IFN-ß and multiple sclerosis: cross-talking of immune cells and integration of immunoregulatory networks.

Multiple sclerosis (MS) is characterized by autoimmune inflammation affecting the central nervous system and subsequent neurodegeneration. Historically, damage was thought to be mediated exclusively by auto-antigen-activated pro-inflammatory T cells. However, more recently, we are gaining increasing knowledge on the pathogenic role played in MS by B cells, dendritic cells and monocytes. IFN-ß therapy was one the first approved therapy for MS for its ability to reduce relapse rate and MRI lesion activity and to significantly decrease risk of disability progression. IFN-ß-mediated mechanisms of action, even if not completely understood, mainly rely on its multifaceted pleiotropic effects resulting in sustained anti-inflammatory properties directed toward almost every immune cell type. Here, we will discuss in detail literature data characterizing the pathogenic activity of the different immune cell subsets involved in MS pathogenesis and how IFN-ß therapy regulates their function by modulating bystander responses. We believe that the effectiveness of this drug in MS treatment, even if in use for a long time, can unveil new insights on this disease and still teach a lesson to researchers in the MS field.