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There is major evidence for the involvement of immunological processes in the pathophysiology of schizophrenia. Especially alterations of T-cell function and activation of the inflammatory response system appear to be linked to schizophrenia. A mild chronic inflammation process has been proposed and repeated findings of altered serum cytokine levels led to the hypothesis of a TH2 shift or cytokine imbalance in schizophrenia. We investigated serum levels of TH1 and TH2 related cytokines and immune markers in 25 patients suffering an acute schizophrenic episode (all unmedicated, 22 neuroleptica-naive) at different stages of disorder (18 first episode, FEP; 7 recurrent episode, REP) compared to 25 age and sex matched healthy controls. In patients, we found an increase of the TH2 system cytokine IL-13 (p = 0.039) and a decrease of the TH1 system markers sICAM-1 (p = 0.011) and sIL-2R (p = 0.063, n. s.). Elevation of the pro-inflammatory cytokine IL-6 was not significant (p = 0.052). The effect of sIL-2R decrease was greater in the FEP subgroup (p = 0.01) of patients. We found no group differences in the other investigated immune markers: IL-4, IL-8, TNF-alpha, and Interferon-gamma, in which most readings were below the lower detection limit of the respective assay. Our findings support the notion of a TH1/TH2 imbalance particularly in the acute manifestation phase of schizophrenia. In the long run, this may lead to the identification of cytokine patterns that are applicable as trait or state markers, may be helpful in making or ensuring diagnosis or in monitoring therapy.

Matrix metalloproteinase-9 (MMP-9) plays an important role in both physiological and pathological processes. This enzyme is a peripheral biomarker of neuroinflammation in multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system. Presently, expensive magnetic resonance imaging (MRI) studies are used to monitor subclinical disease activity in MS. An alternative to costly MRI scans could be the detection of MMP-9, using a low-cost, disposable sensor system for MMP-9 suitable for home-monitoring of inflammation. This would allow an early prediction of the failure of anti-inflammatory therapies and more timely clinical intervention to limit neuronal damage and prevent disability. Herein we present the development of a disposable sensor for fast and straightforward detection of MMP-9. Biosensors were produced by coating electrodes with oxidized dextran and subsequent cross-linking with peptides containing specific cleavage sites for MMP-9. Exposure of the films to the enzyme resulted in the degradation of the films, which was monitored using impedance measurements. Sensor response was rapid, a significant impedance change was usually observed within 5 min after the addition of MMP-9. Sensors showed a negligible response to matrix metalloproteinase-2 (MMP-2), a protease which may interfere with MMP-9 detection. The peptide sequence with the highest sensitivity and selectivity Leu-Gly-Arg-Met-Gly-Leu-Pro-Gly-Lys was selected to construct calibration curves. MMP-9 was successfully detected in a clinically relevant range from 50 to 400 ng/ml. Two different processes of hydrogel degradation were observed on electrode surfaces with different roughness, and both appeared suitable to monitor MMP-9 activity. The sensor materials are generic and can be easily adopted to respond to other proteases by selecting peptide cross-linkers with suitable cleavage sites.

Interest in the role of B-cells in multiple sclerosis (MS) pathogenesis has increased, and a number of B-cell targeted therapies are currently in clinical trials. B-cells are key mediators of the humoral immune response, with roles including antibody production and acting as antigen presenting cells. Whilst previously, the presence of B-cells within MS plaques has been thought to be secondary to T-cell dysregulation, it is now becoming clear that B-cells play an independent role in disease. In this review we will discuss the potential role of B-cells in MS, how this influences our understanding of the disease, and potential therapeutic implications.

Experimental autoimmune encephalomyelitis (EAE) is a Th17-mediated autoimmune disease and an animal model for multiple sclerosis (MS). Complete Freund's adjuvant (CFA) contains pathogen-associated molecular patterns (PAMPs) that bind toll-like receptors (TLRs), and is necessary to induce EAE. Upstream TLR signals modify innate and adaptive immune responses in EAE. In detail, the common TLR adaptor molecule MyD88 is necessary for induction of EAE, and mediates activation of peripheral myeloid dendritic cells (mDCs) and differentiation of autoimmune Th17 cells. The stimulatory TLRs have not yet been identified for Th17 cells. TLR4 down regulates disease severity in EAE and Th17 cell responses, but promotes Th1 cell responses, which may inhibit the differentiation of Th17 cells. Moreover, treatment with a TLR4 ligand tolerizes mice and prevents EAE. TLR9 down regulates disease severity in myelin oligodendrocyte glycoprotein (MOG)-induced EAE, whereas it promotes disease in MOG(35-55)-induced EAE. Thus MyD88, TLR4 and TLR9 modify the disease process in EAE. Both endogenous and CFA-derived TLR ligands are implicated to modulate the disease process.

Background: The N-methyl-D-aspartate receptor (NMDAR) is a type of ionotropic receptor belonging to the glutamate receptor superfamily found abundantly in the cortex, basal ganglia, and sensory pathways of the nervous system. The receptor is highly permeable to calcium ions and plays a key role in the plasticity of synapses, which is believed to underlie memory and learning. The NMDAR has been associated with a range of neurological disorders including ischemic brain damage and epilepsy, andmore speculatively with neurodegenerative disorders such as Alzheimer's and Huntington's chorea. Anti-NMDA receptor encephalitis has been recently identified as treatment responsive encephalitis associatedwith anti-NMDA receptor antibodies (Iizuka and Sakai, 2008). These antibodies bind to the NR1/NR2 heteromers of the NMDAR and antibody levels are known to correlate with the clinical severity of the disease. Clinical features seen in neuropsychiatric disorders such as Tourette's syndrome (TS) overlap with NMDAR receptor encephalitis, which might make it a part of the spectrum of anti-NMDAR disorders. Aims: Pathogenic antibodies against the NMDAR have been implicated in a range of disorders, however, the full clinical spectrum and treatment responses are still unclear. Therefore, in the present study we analysed serum samples from children diagnosed with TS for the presence of anti-NMDAR antibodies. Materials and methods: Sera from 21 TS patients with a mean age of 11 years were analysed for the presence of antibodies against the NMDAR using HEK293 cells transfected with NR1:NR2B subunits and co-transfected with enhanced green fluorescent protein (EGFP). According to the number of cells stained and intensity of staining the samples were scored between 0 and 4 (0= negative, 4= strongly positive). Results: Out of the 21 samples tested in the assay 4 were found positive for antibodies against the NMDAR. All 4 serum samples came frommale patients diagnosed with TS with an age range of 8 to 14 years. Conclusions: In the present study the presence of anti-NMDAR antibodies in the sera of 4 TS patients has been demonstrated. TS is co-morbid with multiple conditions like obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) so an understanding into its pathogenic mechanism would have major implications in the field of neuropsychiatry.