Our aim was to identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of Parkinson’s disease (PD) patients and healthy controls by microarray technology and analysis of related molecular pathways by functional annotation. Thirty PD patients and 30 controls were enrolled. Agilent Human 8X60 K Oligo Microarray was used for gene level expression identification. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein–protein interaction analyses were performed with STRING. Expression levels of randomly selected DEGs were quantified by real time quantitative polymerase chain reaction (RT-PCR) for validation. Flow cytometry was done to determine frequency of regulatory T cells (Tregs) in PBMC. A total of 361 DEGs (143 upregulated and 218 downregulated) were identified after GeneSpring analysis. DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions. Pathway analyses demonstrated that upregulated genes mainly enriched in p53 (CASP3, TSC2, ATR, MDM4, CCNG1) and PI3K/Akt (IL2RA, IL4R, TSC2, VEGFA, PKN2, PIK3CA, ITGA4, BCL2L11) signaling pathways. TP53 and PIK3CA were identified as most significant hub proteins. Expression profiles obtained by RT-PCR were consistent with microarray findings. PD patients showed increased proportions of CD49d+ Tregs, which correlated with disability scores. Survival pathway genes were upregulated putatively to compensate neuronal degeneration. Bioinformatics analysis showed an association between survival and inflammation genes. Increased CD49d+ Treg ratios might signify the effort of the immune system to suppress ongoing neuroinflammation.

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Multiple sclerosis (MS) often starts in the form of clinically isolated syndrome (CIS) and only some of the CIS patients progress to relapsing-remitting MS (RRMS). Biomarkers to predict conversion from CIS to MS are thus greatly needed for making correct treatment decisions. To identify a predictive cerebrospinal fluid (CSF) protein, we analyzed the first-attack CSF samples of CIS patients who converted (CIS-MS) (n = 23) and did not convert (CIS-CIS) (n = 19) to RRMS in a follow-up period of 5 years using proteomics analysis by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and verified by ELISA. Label-free differential proteomics analysis of CSF ensured that 637 proteins were identified and 132 of these proteins were found to be statistically significant. Further investigation with the ingenuity pathway analysis (IPA) software led to identification of three pathway networks mostly comprised proteins involved in inflammatory response, cellular growth and tissue proliferation. CSF levels of four of the most differentially expressed proteins belonging to the cellular proliferation network function, chitinase-3-like protein 1 (CHI3L1), tumor necrosis factor receptor superfamily member 21 (TNFRSF21), homeobox protein Hox-B3 (HOXB3) and iduronate 2-sulfatase (IDS), were measured by ELISA. CSF levels of HOXB3 were significantly increased in CIS-MS patients. Our results indicate that cell and tissue proliferation functions are dysregulated in MS as early as the first clinical episode. HOXB3 has emerged as a potential novel biomarker which might be used for prediction of CIS-MS conversion.

Background:The involvement of inflammation in the pathophysiology of cluster headache (CH) has been suggested, with a role implied for interleukin (IL)-1β. We aimed to measure peripheral blood expression levels of IL-1β-inducing systems, the inflammasome complex, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and investigate their values as putative biomarkers in CH. Methods:In this cross-sectional study conducted in the Headache Unit of Istanbul University, Turkey, blood mononuclear cells (PBMCs) and sera were collected from 30 patients with episodic migraine, 4 with chronic CH, and 47 healthy individuals. Levels of inflammasome complex components (NLRP1, NLRP3, caspase 1, and ASC), end products of inflammasome complex activity (IL-1β, IL-18, and nitric oxide synthase isoforms), neuron-specific enolase, other inflammatory factors (NF-κB, HMGB1, and s100b), and anti-inflammatory IL-4 were measured by real-time quantitative polymerase chain reaction and/or enzyme-linked immunosorbent assay.Results: NLRP3 expression levels were significantly reduced in PBMC samples of patients with CH, obtained during CH attacks (n = 24) or headache-free (out of cycle) episodes (n = 10). CH-attack patients showed greater expression levels of IL-1β (2 −ΔΔCT