Recent progress in omics-driven analysis of MS to unravel pathological mechanisms

References

• Lassmann H, van HJ. The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett. 585(23), 3715–3723 (2011).
   PubMed Web of Science ®Google Scholar
• Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N. Engl. J. Med. 343(13), 938–952 (2000).
   PubMed Web of Science ®Google Scholar
• Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV. Environmental factors and their timing in adult-onset multiple sclerosis. Nat. Rev. Neurol. 6(3), 156–166 (2010).
   PubMed Web of Science ®Google Scholar
• Milo R, Kahana E. Multiple sclerosis: geoepidemiology, genetics and the environment. Autoimmun. Rev. 9(5), A387–A394 (2010).
   PubMed Web of Science ®Google Scholar
• Steinman L. A molecular trio in relapse and remission in multiple sclerosis. Nat. Rev. Immunol. 9(6), 440–447 (2009).
   PubMed Web of Science ®Google Scholar
• Vukusic S, Confavreux C. Prognostic factors for progression of disability in the secondary progressive phase of multiple sclerosis. J. Neurol. Sci. 206(2), 135–137 (2003).
   PubMed Web of Science ®Google Scholar
• Geurts JJ, Stys PK, Minagar A, Amor S, Zivadinov R. Gray matter pathology in (chronic) MS: modern views on an early observation. J. Neurol. Sci. 282(1–2), 12–20 (2009).
   PubMed Web of Science ®Google Scholar
• Henderson AP, Barnett MH, Parratt JD, Prineas JW. Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann. Neurol. 66(6), 739–753 (2009).
   PubMed Web of Science ®Google Scholar
• Ebers GC. Environmental factors and multiple sclerosis. Lancet Neurol. 7(3), 268–277 (2008).
   PubMed Web of Science ®Google Scholar
• Hoppenbrouwers IA, Cortes LM, Aulchenko YS et al. Familial clustering of multiple sclerosis in a Dutch genetic isolate. Mult. Scler. 13(1), 17–24 (2007).
   PubMedGoogle Scholar
• Huynh JL, Casaccia P. Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol. 12(2), 195–206 (2013).
   PubMed Web of Science ®Google Scholar
• Polman CH, Reingold SC, Banwell B et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 69(2), 292–302 (2011).
   PubMed Web of Science ®Google Scholar
• Aktas O, Kieseier B, Hartung HP. Neuroprotection, regeneration and immunomodulation: broadening the therapeutic repertoire in multiple sclerosis. Trends Neurosci. 33(3), 140–152 (2010).
   PubMed Web of Science ®Google Scholar
• Vosoughi R, Freedman MS. Therapy of MS. Clin. Neurol. Neurosurg. 112(5), 365–385 (2010).
   PubMed Web of Science ®Google Scholar
• Junker A. Pathophysiology of translational regulation by microRNAs in multiple sclerosis. FEBS Lett. 585(23), 3738–3746 (2011).
   PubMed Web of Science ®Google Scholar
• Teunissen CE, Dijkstra C, Polman C. Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol. 4(1), 32–41 (2005).
   PubMed Web of Science ®Google Scholar
• Tumani H, Hartung HP, Hemmer B et al. Cerebrospinal fluid biomarkers in multiple sclerosis. Neurobiol. Dis. 35(2), 117–127 (2009).
   PubMed Web of Science ®Google Scholar
• Ziemann U, Wahl M, Hattingen E, Tumani H. Development of biomarkers for multiple sclerosis as a neurodegenerative disorder. Prog. Neurobiol. 95(4), 670–685 (2011).
   PubMed Web of Science ®Google Scholar
• Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69(3), 89–95 (2001).
   PubMed Web of Science ®Google Scholar
• Wang K, Lee I, Carlson G, Hood L, Galas D. Systems biology and the discovery of diagnostic biomarkers. Dis. Markers 28(4), 199–207 (2010).
   PubMed Web of Science ®Google Scholar
• Kemppinen A, Sawcer S, Compston A. Genome-wide association studies in multiple sclerosis: lessons and future prospects. Brief. Funct. Genomics 10(2), 61–70 (2011).
   PubMed Web of Science ®Google Scholar
• Kemppinen AK, Kaprio J, Palotie A, Saarela J. Systematic review of genome-wide expression studies in multiple sclerosis. BMJ Open 1(1), e000053 (2011).
   PubMed Web of Science ®Google Scholar
• Sadovnick AD. Genetic background of multiple sclerosis. Autoimmun. Rev. 11(3), 163–166 (2012).
   PubMed Web of Science ®Google Scholar
• Teunissen CE, Khalil M. Neurofilaments as biomarkers in multiple sclerosis. Mult. Scler. 18(5), 552–556 (2012).
   PubMed Web of Science ®Google Scholar
• Compston A, Coles A. Multiple sclerosis. Lancet 372(9648), 1502–1517 (2008).
   PubMed Web of Science ®Google Scholar
• Hawkes CH, Macgregor AJ. Twin studies and the heritability of MS: a conclusion. Mult. Scler. 15(6), 661–667 (2009).
   PubMed Web of Science ®Google Scholar
• Handel AE, Handunnetthi L, Berlanga AJ, Watson CT, Morahan JM, Ramagopalan SV. The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression. PLoS ONE 5(4), e10142 (2010).
   Web of Science ®Google Scholar
• Peltonen L. Old suspects found guilty – the first genome profile of multiple sclerosis. N. Engl. J. Med. 357(9), 927–929 (2007).
   PubMed Web of Science ®Google Scholar
• National Human Genome Research Institute (NHGRI).
   Google Scholar
• Hindorff LA, Sethupathy P, Junkins HA et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl Acad. Sci. USA 106(23), 9362–9367 (2009).
   PubMed Web of Science ®Google Scholar
• Manolio TA, Brooks LD, Collins FS. A HapMap harvest of insights into the genetics of common disease. J. Clin. Invest 118(5), 1590–1605 (2008).
   PubMed Web of Science ®Google Scholar
• Syvanen AC. Accessing genetic variation: genotyping single nucleotide polymorphisms. Nat. Rev. Genet. 2(12), 930–942 (2001).
   PubMed Web of Science ®Google Scholar
• Wang Z, Moult J. SNPs, protein structure, and disease. Hum. Mutat. 17(4), 263–270 (2001).
   PubMed Web of Science ®Google Scholar
• Ars E, Serra E, Garcia J et al. Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1. Hum. Mol. Genet. 9(2), 237–247 (2000).
   PubMed Web of Science ®Google Scholar
• Pagani F, Baralle FE. Genomic variants in exons and introns: identifying the splicing spoilers. Nat. Rev. Genet. 5(5), 389–396 (2004).
   PubMed Web of Science ®Google Scholar
• Gong J, Tong Y, Zhang HM et al. Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum. Mutat. 33(1), 254–263 (2012).
   PubMed Web of Science ®Google Scholar
• Mattick JS, Makunin IV. Non-coding RNA. Hum. Mol. Genet. 15 Spec No 1, R17–R29 (2006).
   PubMed Web of Science ®Google Scholar
• Mehler MF, Mattick JS. Non-coding RNAs in the nervous system. J. Physiol 575(Pt 2), 333–341 (2006).
   PubMed Web of Science ®Google Scholar
• Chanock S. Candidate genes and single nucleotide polymorphisms (SNPs) in the study of human disease. Dis. Markers 17(2), 89–98 (2001).
   PubMed Web of Science ®Google Scholar
• Negm RS, Verma M, Srivastava S. The promise of biomarkers in cancer screening and detection. Trends Mol. Med. 8(6), 288–293 (2002).
   PubMed Web of Science ®Google Scholar
• Sawcer S, Hellenthal G, Pirinen M et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476(7359), 214–219 (2011).
   PubMed Web of Science ®Google Scholar
• Gourraud PA, Harbo HF, Hauser SL, Baranzini SE. The genetics of multiple sclerosis: an up-to-date review. Immunol. Rev. 248(1), 87–103 (2012).
   PubMed Web of Science ®Google Scholar
• Moonesinghe R, Liu T, Khoury MJ. Evaluation of the discriminative accuracy of genomic profiling in the prediction of common complex diseases. Eur. J. Hum. Genet. 18(4), 485–489 (2010).
   PubMed Web of Science ®Google Scholar
• Moonesinghe R, Khoury MJ, Liu T, Janssens AC. Discriminative accuracy of genomic profiling comparing multiplicative and additive risk models. Eur. J. Hum. Genet. 19(2), 180–185 (2011).
   PubMed Web of Science ®Google Scholar
• Lundmark F, Duvefelt K, Iacobaeus E et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat. Genet. 39(9), 1108–1113 (2007).
   PubMed Web of Science ®Google Scholar
• Gregory SG, Schmidt S, Seth P et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 39(9), 1083–1091 (2007).
   PubMed Web of Science ®Google Scholar
• Babron MC, Perdry H, Handel AE et al. Determination of the real effect of genes identified in GWAS: the example of IL2RA in multiple sclerosis. Eur. J. Hum. Genet. 20(3), 321–325 (2012).
   PubMed Web of Science ®Google Scholar
• Fry TJ, Mackall CL. Interleukin-7: from bench to clinic. Blood 99(11), 3892–3904 (2002).
   PubMed Web of Science ®Google Scholar
• O'Doherty C, Alloza I, Rooney M, Vandenbroeck K. IL7RA polymorphisms and chronic inflammatory arthropathies. Tissue Antigens 74(5), 429–431 (2009).
   PubMedGoogle Scholar
• Cantrell DA, Smith KA. The interleukin-2 T-cell system: a new cell growth model. Science 224(4655), 1312–1316 (1984).
   PubMed Web of Science ®Google Scholar
• Stern JB, Smith KA. Interleukin-2 induction of T-cell G1 progression and c-myb expression. Science 233(4760), 203–206 (1986).
   PubMed Web of Science ®Google Scholar
• Noguchi M, Nakamura Y, Russell SM et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science 262(5141), 1877–1880 (1993).
   PubMed Web of Science ®Google Scholar
• Qu HQ, Verlaan DJ, Ge B et al. A cis-acting regulatory variant in the IL2RA locus. J. Immunol. 183(8), 5158–5162 (2009).
   PubMed Web of Science ®Google Scholar
• Matesanz F, Gonzalez-Perez A, Lucas M et al. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1. PLoS ONE 7(5), e36140 (2012).
   Web of Science ®Google Scholar
• Libioulle C, Louis E, Hansoul S et al. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 3(4), e58 (2007).
   PubMed Web of Science ®Google Scholar
• De Jager PL, Jia X, Wang J et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat. Genet. 41(7), 776–782 (2009).
   PubMed Web of Science ®Google Scholar
• Zimecki M. Potential therapeutic interventions via EP2/EP4 prostaglandin receptors. Postepy Hig. Med. Dosw. (Online) 66, 287–294 (2012).
   PubMedGoogle Scholar
• Gregory AP, Dendrou CA, Attfield KE et al. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature 488(7412), 508–511 (2012).
   PubMed Web of Science ®Google Scholar
• van Oosten BW, Barkhof F, Truyen L et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47(6), 1531–1534 (1996).
   PubMed Web of Science ®Google Scholar
• Bahlo M. Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat. Genet. 41(7), 824–828 (2009).
   PubMed Web of Science ®Google Scholar
• Blanco-Kelly F, Matesanz F, Alcina A et al. CD40: novel association with Crohn's disease and replication in multiple sclerosis susceptibility. PLoS ONE 5(7), e11520 (2010).
   PubMed Web of Science ®Google Scholar
• Castro MA, Oliveira MI, Nunes RJ et al. Extracellular isoforms of CD6 generated by alternative splicing regulate targeting of CD6 to the immunological synapse. J. Immunol. 178(7), 4351–4361 (2007).
   PubMed Web of Science ®Google Scholar
• Kofler DM, Severson CA, Mousissian N, De Jager PL, Hafler DA. The CD6 multiple sclerosis susceptibility allele is associated with alterations in CD4+ T cell proliferation. J. Immunol. 187(6), 3286–3291 (2011).
   PubMed Web of Science ®Google Scholar
• Swaminathan B, Cuapio A, Alloza I et al. Fine mapping and functional analysis of the multiple sclerosis risk gene CD6. PLoS ONE 8(4), e62376 (2013).
   Web of Science ®Google Scholar
• Chatzigeorgiou A, Lyberi M, Chatzilymperis G, Nezos A, Kamper E. CD40/CD40L signaling and its implication in health and disease. Biofactors 35(6), 474–483 (2009).
   PubMed Web of Science ®Google Scholar
• Ferrer IR, Liu D, Pinelli DF, Koehn BH, Stempora LL, Ford ML. CD40/CD154 blockade inhibits dendritic cell expression of inflammatory cytokines but not costimulatory molecules. J. Immunol. 189(9), 4387–4395 (2012).
   PubMed Web of Science ®Google Scholar
• Rodriguez-Rodriguez L, Castaneda S, Vazquez-Rodriguez TR et al. Influence of CD40 rs1883832 polymorphism in susceptibility to and clinical manifestations of biopsy-proven giant cell arteritis. J. Rheumatol. 37(10), 2076–2080 (2010).
   PubMed Web of Science ®Google Scholar
• Kierdorf K, Prinz M. Factors regulating microglia activation. Front Cell Neurosci. 7, 44 (2013).
   PubMed Web of Science ®Google Scholar
• Banerjee S, Lu J, Cai Q et al. The EBV latent antigen 3C inhibits apoptosis through targeted regulation of interferon regulatory factors 4 and 8. PLoS Pathog. 9(5), e1003314 (2013).
   Web of Science ®Google Scholar
• Crosslin DR, McDavid A, Weston N et al. Genetic variation associated with circulating monocyte count in the eMERGE Network. Hum. Mol. Genet. 22(10), 2119–2127 (2013).
   PubMed Web of Science ®Google Scholar
• The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study. PLoS ONE 6(4), e18813 (2011).
   Web of Science ®Google Scholar
• Alcina A, Fernandez O, Gonzalez JR et al. Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis. Eur. J. Hum. Genet. 18(7), 827–831 (2010).
   PubMed Web of Science ®Google Scholar
• Varade J, Comabella M, Ortiz MA et al. Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CBLB [correction of CLBL] genes. Mult. Scler. 18(7), 959–965 (2012).
   PubMed Web of Science ®Google Scholar
• Corrado L, Bergamaschi L, Barizzone N et al. Association of the CBLB gene with multiple sclerosis: new evidence from a replication study in an Italian population. J. Med. Genet. 48(3), 210–211 (2011).
   PubMed Web of Science ®Google Scholar
• Faitar SL, Dabbeekeh JT, Ranalli TA, Cowell JK. EVI5 is a novel centrosomal protein that binds to alpha- and gamma-tubulin. Genomics 86(5), 594–605 (2005).
   PubMed Web of Science ®Google Scholar
• Eldridge AG, Loktev AV, Hansen DV, Verschuren EW, Reimann JD, Jackson PK. The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1. Cell 124(2), 367–380 (2006).
   PubMed Web of Science ®Google Scholar
• Venuprasad K. Cbl-b and itch: key regulators of peripheral T-cell tolerance. Cancer Res. 70(8), 3009–3012 (2010).
   PubMed Web of Science ®Google Scholar
• Qiao G, Lei M, Li Z et al. Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B. J. Immunol. 179(7), 4473–4479 (2007).
   PubMed Web of Science ®Google Scholar
• Guo H, Qiao G, Ying H et al. E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity. Cell Rep. 1(5), 472–482 (2012).
   PubMed Web of Science ®Google Scholar
• Johnson BA, Wang J, Taylor EM et al. Multiple sclerosis susceptibility alleles in African Americans. Genes Immun. 11(4), 343–350 (2010).
   PubMed Web of Science ®Google Scholar
• Denecke B, Meyerdierks A, Bottger EC. RGS1 is expressed in monocytes and acts as a GTPase-activating protein for G-protein-coupled chemoattractant receptors. J. Biol. Chem. 274(38), 26860–26868 (1999).
   PubMed Web of Science ®Google Scholar
• Han JI, Huang NN, Kim DU, Kehrl JH. RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization. J. Leukoc. Biol. 79(6), 1357–1368 (2006).
   PubMed Web of Science ®Google Scholar
• Cotsapas C, Voight BF, Rossin E et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. 7(8), e1002254- (2011).
   Web of Science ®Google Scholar
• Bird A. Perceptions of epigenetics. Nature 447(7143), 396–398 (2007).
   PubMed Web of Science ®Google Scholar
• Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 23(7), 781–783 (2009).
   PubMed Web of Science ®Google Scholar
• Saetrom P, Snove O, Jr., Rossi JJ. Epigenetics and microRNAs. Pediatr. Res. 61(5 Pt 2), 17R–23R (2007).
   PubMedGoogle Scholar
• Liu L, Li Y, Tollefsbol TO. Gene-environment interactions and epigenetic basis of human diseases. Curr. Issues Mol. Biol. 10(1–2), 25–36 (2008).
   PubMedGoogle Scholar
• Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296(23), 2832–2838 (2006).
   PubMed Web of Science ®Google Scholar
• Ramagopalan SV, Heger A, Berlanga AJ et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 20(10), 1352–1360 (2010).
   PubMed Web of Science ®Google Scholar
• Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN. Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription. J. Biol. Chem. 276(44), 40614–40620 (2001).
   PubMed Web of Science ®Google Scholar
• Giangreco AA, Vaishnav A, Wagner D et al. Tumor Suppressor microRNAs, miR-100 and -125b, Are Regulated by 1,25-dihydroxyvitamin D in Primary Prostate Cells and in Patient Tissue. Cancer Prev. Res. (Phila) 6(5), 483–494 (2013).
   PubMed Web of Science ®Google Scholar
• Lisse TS, Chun RF, Rieger S, Adams JS, Hewison M. Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts. J. Bone Miner. Res. (2013).
   Web of Science ®Google Scholar
• Mohri T, Nakajima M, Takagi S, Komagata S, Yokoi T. MicroRNA regulates human vitamin D receptor. Int. J. Cancer 125(6), 1328–1333 (2009).
   PubMed Web of Science ®Google Scholar
• Pereira F, Barbachano A, Singh PK, Campbell MJ, Munoz A, Larriba MJ. Vitamin D has wide regulatory effects on histone demethylase genes. Cell Cycle 11(6), 1081–1089 (2012).
   PubMed Web of Science ®Google Scholar
• Baranzini SE, Mudge J, van Velkinburgh JC et al. Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature 464(7293), 1351–1356 (2010).
   PubMed Web of Science ®Google Scholar
• Cuzin F, Rassoulzadegan M. Non-Mendelian epigenetic heredity: gametic RNAs as epigenetic regulators and transgenerational signals. Essays Biochem. 48(1), 101–106 (2010).
   PubMedGoogle Scholar
• Geeleher P, Huang SR, Gamazon ER, Golden A, Seoighe C. The regulatory effect of miRNAs is a heritable genetic trait in humans. BMC Genomics 13, 383 (2012).
   PubMed Web of Science ®Google Scholar
• Meikar O, Da RM, Kotaja N. Epigenetic regulation of male germ cell differentiation. Subcell Biochem. 61, 119–138 (2012).
   Google Scholar
• Etheridge A, Lee I, Hood L, Galas D, Wang K. Extracellular microRNA: a new source of biomarkers. Mutat. Res. 717(1–2), 85–90 (2011).
   PubMed Web of Science ®Google Scholar
• Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat. Rev. Genet. 13(5), 358–369 (2012).
   PubMed Web of Science ®Google Scholar
• Keller A, Leidinger P, Lange J et al. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS ONE 4(10), e7440 (2009).
   PubMed Web of Science ®Google Scholar
• Cox MB, Cairns MJ, Gandhi KS et al. MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS ONE 5(8), e12132 (2010).
   PubMed Web of Science ®Google Scholar
• De SG, Ferracin M, Biondani A et al. Altered miRNA expression in T regulatory cells in course of multiple sclerosis. J. Neuroimmunol. 226(1–2), 165–171 (2010).
   PubMed Web of Science ®Google Scholar
• Gandhi R, Healy B, Gholipour T et al. Circulating microRNAs as biomarkers for disease staging in multiple sclerosis. Ann. Neurol. (2013).
   PubMed Web of Science ®Google Scholar
• Haghikia A, Haghikia A, Hellwig K et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: a case-control study. Neurology 79(22), 2166–2170 (2012).
   PubMed Web of Science ®Google Scholar
• Lindberg RL, Hoffmann F, Mehling M, Kuhle J, Kappos L. Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur. J. Immunol. 40(3), 888–898 (2010).
   PubMed Web of Science ®Google Scholar
• Martinelli-Boneschi F, Fenoglio C, Brambilla P et al. MicroRNA and mRNA expression profile screening in multiple sclerosis patients to unravel novel pathogenic steps and identify potential biomarkers. Neurosci. Lett. 508(1), 4–8 (2012).
   PubMed Web of Science ®Google Scholar
• Sievers C, Meira M, Hoffmann F, Fontoura P, Kappos L, Lindberg RL. Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects. Clin. Immunol. 144(1), 70–79 (2012).
   PubMed Web of Science ®Google Scholar
• Waschbisch A, Atiya M, Linker RA, Potapov S, Schwab S, Derfuss T. Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis. PLoS ONE 6(9), e24604 (2011).
   PubMed Web of Science ®Google Scholar
• Dahlgaard J, Mazin W, Jensen T et al. Analytical variables influencing the performance of a miRNA based laboratory assay for prediction of relapse in stage I non-small cell lung cancer (NSCLC). BMC Res. Notes 4, 424 (2011).
   PubMedGoogle Scholar
• McDonald JS, Milosevic D, Reddi HV, Grebe SK, Algeciras-Schimnich A. Analysis of circulating microRNA: preanalytical and analytical challenges. Clin. Chem. 57(6), 833–840 (2011).
   PubMed Web of Science ®Google Scholar
• Chen JA, Huang YP, Mazzoni EO, Tan GC, Zavadil J, Wichterle H. Mir-17-3p controls spinal neural progenitor patterning by regulating Olig2/Irx3 cross-repressive loop. Neuron 69(4), 721–735 (2011).
   PubMed Web of Science ®Google Scholar
• Kuhlmann T, Miron V, Cui Q, Wegner C, Antel J, Bruck W. Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain 131(Pt 7), 1749–1758 (2008).
   PubMed Web of Science ®Google Scholar
• Cichocki F, Felices M, McCullar V et al. Cutting edge: microRNA-181 promotes human NK cell development by regulating Notch signaling. J. Immunol. 187(12), 6171–6175 (2011).
   PubMed Web of Science ®Google Scholar
• Wang P, Gu Y, Zhang Q et al. Identification of resting and type I IFN-activated human NK cell miRNomes reveals microRNA-378 and microRNA-30e as negative regulators of NK cell cytotoxicity. J. Immunol. 189(1), 211–221 (2012).
   PubMed Web of Science ®Google Scholar
• Chanvillard C, Jacolik RF, Infante-Duarte C, Nayak RC. The role of natural killer cells in multiple sclerosis and their therapeutic implications. Front Immunol. 4, 63 (2013).
   PubMed Web of Science ®Google Scholar
• Wang X, Gocek E, Liu CG, Studzinski GP. MicroRNAs181 regulate the expression of p27Kip1 in human myeloid leukemia cells induced to differentiate by 1,25-dihydroxyvitamin D3. Cell Cycle 8(5), 736–741 (2009).
   PubMed Web of Science ®Google Scholar
• Li G, Yu M, Lee WW et al. Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat. Med. 18(10), 1518–1524 (2012).
   PubMed Web of Science ®Google Scholar
• Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139(4), 693–706 (2009).
   PubMed Web of Science ®Google Scholar
• Kumar M, Ahmad T, Sharma A et al. Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J. Allergy Clin. Immunol. 128(5), 1077–1085 (2011).
   PubMed Web of Science ®Google Scholar
• Swaminathan S, Suzuki K, Seddiki N et al. Differential regulation of the Let-7 family of microRNAs in CD4+ T cells alters IL-10 expression. J. Immunol. 188(12), 6238–6246 (2012).
   PubMed Web of Science ®Google Scholar
• Ridolfi E, Fenoglio C, Cantoni C et al. Expression and genetic analysis of microRNAs involved in multiple sclerosis. Int. J. Mol. Sci. 14(3), 4375–4384 (2013).
   PubMed Web of Science ®Google Scholar
• Sun W, Shen W, Yang S, Hu F, Li H, Zhu TH. miR-223 and miR-142 attenuate hematopoietic cell proliferation, and miR-223 positively regulates miR-142 through LMO2 isoforms and CEBP-beta. Cell Res. 20(10), 1158–1169 (2010).
   PubMed Web of Science ®Google Scholar
• Rio P, Agirre X, Garate L et al. Down-regulated expression of hsa-miR-181c in Fanconi anemia patients: implications in TNFalpha regulation and proliferation of hematopoietic progenitor cells. Blood 119(13), 3042–3049 (2012).
   PubMed Web of Science ®Google Scholar
• Huang B, Zhao J, Lei Z et al. miR-142-3p restricts cAMP production in CD4+. EMBO Rep. 10(2), 180–185 (2009).
   PubMed Web of Science ®Google Scholar
• Bopp T, Becker C, Klein M et al. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J. Exp. Med. 204(6), 1303–1310 (2007).
   PubMed Web of Science ®Google Scholar
• Yang M, Chen J, Su F et al. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol. Cancer 10, 117 (2011).
   PubMed Web of Science ®Google Scholar
• Bauernfeind F, Rieger A, Schildberg FA, Knolle PA, Schmid-Burgk JL, Hornung V. NLRP3 inflammasome activity is negatively controlled by miR-223. J. Immunol. 189(8), 4175–4181 (2012).
   PubMed Web of Science ®Google Scholar
• Haneklaus M, Gerlic M, Kurowska-Stolarska M et al. Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production. J. Immunol. 189(8), 3795–3799 (2012).
   PubMed Web of Science ®Google Scholar
• Xu W, Presnell SR, Parrish-Novak J et al. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Proc. Natl Acad. Sci.USA 98(17), 9511–9516 (2001).
   PubMed Web of Science ®Google Scholar
• Nakasa T, Miyaki S, Okubo A et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 58(5), 1284–1292 (2008).
   PubMed Web of Science ®Google Scholar
• Tang Y, Luo X, Cui H et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum. 60(4), 1065–1075 (2009).
   PubMed Web of Science ®Google Scholar
• Iyer A, Zurolo E, Prabowo A et al. MicroRNA-146a: a key regulator of astrocyte-mediated inflammatory response. PLoS ONE 7(9), e44789 (2012).
   PubMed Web of Science ®Google Scholar
• Banks RE, Dunn MJ, Hochstrasser DF et al. Proteomics: new perspectives, new biomedical opportunities. Lancet 356(9243), 1749–1756 (2000).
   PubMed Web of Science ®Google Scholar
• Comabella M, Fernandez M, Martin R et al. Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain 133(Pt 4), 1082–1093 (2010).
   PubMed Web of Science ®Google Scholar
• Kroksveen AC, Aasebo E, Vethe H et al. Discovery and initial verification of differentially abundant proteins between multiple sclerosis patients and controls using iTRAQ and SID-SRM. J. Proteomic. 78, 312–325 (2013).
   PubMed Web of Science ®Google Scholar
• Ottervald J, Franzen B, Nilsson K et al. Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers. J. Proteomic. 73(6), 1117–1132 (2010).
   PubMed Web of Science ®Google Scholar
• Teunissen CE, Koel-Simmelink MJ, Pham TV et al. Identification of biomarkers for diagnosis and progression of MS by MALDI-TOF mass spectrometry. Mult. Scler. 17(7), 838–850 (2011).
   PubMed Web of Science ®Google Scholar
• Stoop MP, Singh V, Dekker LJ et al. Proteomics comparison of cerebrospinal fluid of relapsing remitting and primary progressive multiple sclerosis. PLoS ONE 5(8), e12442 (2010).
   Web of Science ®Google Scholar
• Tumani H, Brettschneider J. Biochemical markers of autoimmune diseases of the nervous system. Curr. Pharm. Des 18(29), 4556–4563 (2012).
   PubMed Web of Science ®Google Scholar
• Stoop MP, Dekker LJ, Titulaer MK et al. Quantitative matrix-assisted laser desorption ionization-fourier transform ion cyclotron resonance (MALDI-FT-ICR) peptide profiling and identification of multiple-sclerosis-related proteins. J. Proteome. Res. 8(3), 1404–1414 (2009).
   PubMed Web of Science ®Google Scholar
• Teunissen CE, Tumani H, Bennett JL et al. Consensus guidelines for CSF and blood biobanking for CNS biomarker studies. Mult. Scler. Int. 2011, 246412 (2011).
   PubMedGoogle Scholar
• Ingram G, Hakobyan S, Hirst CL et al. Complement regulator factor H as a serum biomarker of multiple sclerosis disease state. Brain 133(Pt 6), 1602–1611 (2010).
   PubMedGoogle Scholar
• Ingram G, Hakobyan S, Robertson NP, Morgan BP. Elevated plasma C4a levels in multiple sclerosis correlate with disease activity. J. Neuroimmunol. 223(1–2), 124–127 (2010).
   PubMed Web of Science ®Google Scholar
• Ingram G, Hakobyan S, Hirst CL et al. Systemic complement profiling in multiple sclerosis as a biomarker of disease state. Mult. Scler. 18(10), 1401–1411 (2012).
   PubMed Web of Science ®Google Scholar
• Janssen BJ, Huizinga EG, Raaijmakers HC et al. Structures of complement component C3 provide insights into the function and evolution of immunity. Nature 437(7058), 505–511 (2005).
   PubMed Web of Science ®Google Scholar
• Veerhuis R, Nielsen HM, Tenner AJ. Complement in the brain. Mol. Immunol. 48(14), 1592–1603 (2011).
   PubMed Web of Science ®Google Scholar
• Schwab C, McGeer PL. Complement activated C4d immunoreactive oligodendrocytes delineate small cortical plaques in multiple sclerosis. Exp. Neurol. 174(1), 81–88 (2002).
   PubMed Web of Science ®Google Scholar
• Hosokawa M, Klegeris A, Maguire J, McGeer PL. Expression of complement messenger RNAs and proteins by human oligodendroglial cells. Glia 42(4), 417–423 (2003).
   PubMed Web of Science ®Google Scholar
• Jones SE, Jomary C. Clusterin. Int. J. Biochem. Cell Biol. 34(5), 427–431 (2002).
   PubMed Web of Science ®Google Scholar
• Dati G, Quattrini A, Bernasconi L et al. Beneficial effects of r-h-CLU on disease severity in different animal models of peripheral neuropathies. J. Neuroimmunol. 190(1–2), 8–17 (2007).
   PubMed Web of Science ®Google Scholar
• Canto E, Reverter F, Morcillo-Suarez C et al. Chitinase 3-like 1 plasma levels are increased in patients with progressive forms of multiple sclerosis. Mult. Scler. 18(7), 983–990 (2012).
   PubMed Web of Science ®Google Scholar
• Lee CG, Da Silva CA, Dela Cruz CS et al. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu. Rev. Physiol. 73, 479–501 (2011).
   PubMed Web of Science ®Google Scholar
• Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan. Med. Bull. 53(2), 172–209 (2006).
   PubMed Web of Science ®Google Scholar
• Correale J, Fiol M. Chitinase effects on immune cell response in neuromyelitis optica and multiple sclerosis. Mult. Scler. 17(5), 521–531 (2011).
   PubMed Web of Science ®Google Scholar
• Bonneh-Barkay D, Bissel SJ, Kofler J, Starkey A, Wang G, Wiley CA. Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. Brain Pathol. 22(4), 530–546 (2012).
   PubMed Web of Science ®Google Scholar
• Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr. Rev. 22(2), 184–204 (2001).
   PubMed Web of Science ®Google Scholar
• Scarisbrick IA, Radulovic M, Burda JE et al. Kallikrein 6 is a novel molecular trigger of reactive astrogliosis. Biol. Chem. 393(5), 355–367 (2012).
   PubMed Web of Science ®Google Scholar
• Scarisbrick IA, Blaber SI, Lucchinetti CF, Genain CP, Blaber M, Rodriguez M. Activity of a newly identified serine protease in CNS demyelination. Brain 125(Pt 6), 1283–1296 (2002).
   PubMedGoogle Scholar
• Vandell AG, Larson N, Laxmikanthan G et al. Protease-activated receptor dependent and independent signaling by kallikreins 1 and 6 in CNS neuron and astroglial cell lines. J. Neurochem. 107(3), 855–870 (2008).
   PubMed Web of Science ®Google Scholar
• Noorbakhsh F, Vergnolle N, Hollenberg MD, Power C. Proteinase-activated receptors in the nervous system. Nat. Rev. Neurosci. 4(12), 981–990 (2003).
   PubMed Web of Science ®Google Scholar
• Steinhoff M, Vergnolle N, Young SH et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat. Med. 6(2), 151–158 (2000).
   PubMed Web of Science ®Google Scholar
• Hutchinson S, Luo LY, Yousef GM, Soosaipillai A, Diamandis EP. Purification of human kallikrein 6 from biological fluids and identification of its complex with alpha(1)-antichymotrypsin. Clin. Chem. 49(5), 746–751 (2003).
   PubMed Web of Science ®Google Scholar
• Gopalan SM, Wilczynska KM, Konik BS, Bryan L, Kordula T. Nuclear factor-1-X regulates astrocyte-specific expression of the alpha1-antichymotrypsin and glial fibrillary acidic protein genes. J. Biol. Chem. 281(19), 13126–13133 (2006).
   PubMed Web of Science ®Google Scholar
• Rehman AA, Ahsan H, Khan FH. Alpha-2-macroglobulin: A physiological guardian. J. Cell Physiol. 228(8), 1665–1675 (2013).
   PubMed Web of Science ®Google Scholar
• Kordula T, Rydel RE, Brigham EF, Horn F, Heinrich PC, Travis J. Oncostatin M and the interleukin-6 and soluble interleukin-6 receptor complex regulate alpha1-antichymotrypsin expression in human cortical astrocytes. J. Biol. Chem. 273(7), 4112–4118 (1998).
   PubMed Web of Science ®Google Scholar
• Kordula T, Bugno M, Rydel RE, Travis J. Mechanism of interleukin-1- and tumor necrosis factor alpha-dependent regulation of the alpha 1-antichymotrypsin gene in human astrocytes. J. Neurosci. 20(20), 7510–7516 (2000).
   PubMed Web of Science ®Google Scholar
• Bader M. Tissue renin-angiotensin-aldosterone systems: targets for pharmacological therapy. Annu. Rev. Pharmacol. Toxicol. 50, 439–465 (2010).
   PubMed Web of Science ®Google Scholar
• Cuadra AE, Shan Z, Sumners C, Raizada MK. A current view of brain renin-angiotensin system: is the (pro)renin receptor the missing link? Pharmacol. Ther. 125(1), 27–38 (2010).
   PubMed Web of Science ®Google Scholar
• Gollan L, Salomon D, Salzer JL, Peles E. Caspr regulates the processing of contactin and inhibits its binding to neurofascin. J. Cell Biol. 163(6), 1213–1218 (2003).
   PubMed Web of Science ®Google Scholar
• Lamprianou S, Chatzopoulou E, Thomas JL, Bouyain S, Harroch S. A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells. Proc. Natl Acad. Sci. USA 108(42), 17498–17503 (2011).
   PubMed Web of Science ®Google Scholar
• Pedraza L, Huang JK, Colman DR. Organizing principles of the axoglial apparatus. Neuron 30(2), 335–344 (2001).
   PubMed Web of Science ®Google Scholar
• Teunissen C, Menge T, Altintas A et al. Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis. Mult. Scler. (2013).
   Web of Science ®Google Scholar
• Mattsson N, Yaong M, Rosengren L et al. Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in multiple sclerosis. J. Intern. Med. 265(4), 459–464 (2009).
   PubMed Web of Science ®Google Scholar
• Kalinski P. Regulation of immune responses by prostaglandin E2. J. Immunol. 188(1), 21–28 (2012).
   PubMed Web of Science ®Google Scholar
• Khademi M, Kockum I, Andersson ML et al. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course. Mult. Scler. 17(3), 335–343 (2011).
   PubMed Web of Science ®Google Scholar
• Krumbholz M, Theil D, Cepok S et al. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129(Pt 1), 200–211 (2006).
   PubMed Web of Science ®Google Scholar
• Janssens AC, van Duijn CM. Genome-based prediction of common diseases: advances and prospects. Hum. Mol. Genet. 17(R2), R166–R173 (2008).
   PubMedGoogle Scholar