CD3<sup>-</sup>CD56<sup>+</sup> NK cells display an inflammatory profile in RR-MS patients.

Multiple Sclerosis (MS) is an immune-mediated and neurodegenerative disease of central nervous system. Relapsing-remitting (RR)-MS occurring with acute attacks and remissions, is the most common clinical type of MS. There are different strategies applied in first-line treatment of RR-MS patients such as interferon-beta (IFN-beta) and glatiramer acetate. In this study, activating and inhibitory receptor expressions and interleukin (IL)-22 levels of NK cells were investigated in RR-MS patients with or without IFN-beta therapy. Activating receptor expression and IL-22 levels of NK cells were increased in RR-MS patients under IFN-beta therapy. Elevated NK cells with activating profile and increased IL-22 under IFN-beta therapy suggest that IFN-beta treatment might direct NK cells toward a pro-inflammatory status

CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10(-5)) which is important in the immune cell migration, renin-angiotensin (p=6.88x10(-5)) system that induces Th17 dependent immunity, notch signaling (p=1.83x10(-10)) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10(-5)). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications