title: Biomarkers in Multiple Sclerosis: An Up-to-Date Overview.
abstract: During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the most important characteristics that a biomarker must possess in order to be considered as reliable. Additionally, up-to-date biomarkers are further divided into three subgroups, genetic-immunogenetic, laboratorial, and imaging. The most important representatives of each category are presented in the text and for the first time in a summarizing workable table, in a critical way, estimating their diagnostic potential and their efficacy to correlate with phenotypical expression, neuroinflammation, neurodegeneration, disability, and therapeutical response. Special attention is given to the "gold standards" of each category, like HLA-DRB1∗ polymorphisms, oligoclonal bands, vitamin D, and conventional and nonconventional imaging techniques. Moreover, not adequately established but quite promising, recently characterized biomarkers, like TOB-1 polymorphisms, are further discussed.
authors: Immunogenetics Laboratory, 1st Department of Neurology, Aeginition Hospital, National and Kapodistrian University of Athens, 115 28 Athens, Greece.
authors: Serafeim
authors: S
authors: Katsavos
authors: Maria
authors: M
authors: Anagnostouli
references: Neurology. 2007 Jan 23;68(4):283-7
references: 17242333
references: Annu Rev Pharmacol Toxicol. 2001;41:347-66
references: 11264461
references: J Neurol Neurosurg Psychiatry. 2005 Oct;76(10):1377-81
references: 16170080
references: J Clin Invest. 2005 May;115(5):1352-60
references: 15841210
references: Tissue Antigens. 2001 May;57(5):447-56
references: 11556969
references: Neurology. 2008 Mar 25;70(13 Pt 2):1079-83
references: 17881717
references: J Neurol. 2008 Jul;255(7):1023-31
references: 18535872
references: Neurology. 2012 May 1;78(18):1383-9
references: 22517095
references: Arch Neurol. 2010 Sep;67(9):1102-8
references: 20837855
references: Neurobiol Dis. 2009 Aug;35(2):117-27
references: 19426803
references: AJNR Am J Neuroradiol. 2012 Sep;33(8):1586-90
references: 22442041
references: Clin Chim Acta. 2005 Jun;356(1-2):95-101
references: 15878466
references: Acta Neurol Scand Suppl. 2013;(196):16-23
references: 23190287
references: Neurology. 2010 Jul 20;75(3):208-16
references: 20644148
references: Tissue Antigens. 2009 Jul;74(1):17-21
references: 19392788
references: J Neurol Neurosurg Psychiatry. 2006 Jan;77(1):51-5
references: 16361592
references: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11839-44
references: 18689680
references: J Neurol Sci. 1995 Aug;131(2):144-9
references: 7595639
references: Arch Neurol. 2011 Apr;68(4):480-7
references: 21482927
references: J Neurol Sci. 2006 Feb 15;241(1-2):25-9
references: 16316662
references: Eur J Immunol. 2007 Nov;37(11):3229-39
references: 17918203
references: J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):206-11
references: 15654034
references: Mult Scler. 2010 Oct;16(10):1189-92
references: 20685767
references: Clin Neurophysiol. 2012 Feb;123(2):406-10
references: 21778106
references: Sleep Med. 2009 Jan;10(1):129-33
references: 18207455
references: Neurology. 2003 Dec 23;61(12):1720-5
references: 14694036
references: Acta Neurol Scand. 2009 Jan;119(1):39-44
references: 18573131
references: J Neurochem. 2012 Jun;121(5):730-7
references: 21777246
references: Immunology. 2009 Sep;128(1 Suppl):e451-61
references: 19191913
references: J Neuroinflammation. 2012 Sep 17;9:217
references: 22985464
references: Neurology. 2012 Jul 17;79(3):267-73
references: 22700809
references: J Neurol Neurosurg Psychiatry. 2009 May;80(5):575-7
references: 19372295
references: Ann Neurol. 2009 Jun;65(6):639-49
references: 19557869
references: J Immunol. 2008 Jan 15;180(2):1258-67
references: 18178866
references: Lancet Neurol. 2005 Jan;4(1):32-41
references: 15620855
references: AJNR Am J Neuroradiol. 2002 Jun-Jul;23(6):985-8
references: 12063230
references: Brain. 2002 Jul;125(Pt 7):1462-73
references: 12076997
references: J Neuroimmunol. 2002 Nov;132(1-2):180-8
references: 12417449
references: Curr Alzheimer Res. 2012 Dec;9(10):1119-25
references: 22742854
references: Clin Neurophysiol. 2012 Sep;123(9):1872-9
references: 22418590
references: J Neurol. 2005 Feb;252(2):146-50
references: 15729518
references: Neurophysiol Clin. 2011 Oct;41(4):161-71
references: 22078728
references: Ann Neurol. 2009 Dec;66(6):833-42
references: 20033986
references: Fluids Barriers CNS. 2012 Aug 07;9(1):15
references: 22870943
references: J Neuroinflammation. 2011 Jun 03;8:63
references: 21639880
references: Acta Neurol Scand. 1999 Jun;99(6):387-92
references: 10577274
references: Mult Scler. 1998 Jun;4(3):228-31
references: 9762679
references: Neuroimage. 2011 May 1;56(1):21-6
references: 21338694
references: Mult Scler. 2006 Apr;12(2):143-8
references: 16629417
references: J Neuroimmunol. 2012 Jul 15;248(1-2):23-31
references: 22626445
references: Neurol Sci. 2012 Aug;33(4):887-92
references: 22120189
references: J Neuroinflammation. 2012 Sep 14;9:215
references: 22978757
references: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11064-9
references: 15263096
references: Curr Opin Neurol. 2012 Jun;25(3):231-8
references: 22487571
references: Trends Immunol. 2012 Dec;33(12):579-89
references: 22926201
references: Clin Chim Acta. 2012 Nov 20;413(23-24):1813-6
references: 22814197
references: Ann Neurol. 2011 Jan;69(1):83-9
references: 21280078
references: N Engl J Med. 2002 Jan 17;346(3):158-64
references: 11796849
references: Ann Neurol. 2006 Jun;59(6):880-92
references: 16718690
references: J Neurol. 2005 Apr;252(4):396-402
references: 15778816
references: Neurology. 2010 Jun 8;74(23):1868-76
references: 20530323
references: PLoS Genet. 2009 Feb;5(2):e1000369
references: 19197344
references: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7542-7
references: 19380721
references: PLoS One. 2012;7(7):e40443
references: 22792325
references: Mult Scler. 2011 Jan;17(1):16-23
references: 20937631
references: Mult Scler. 2008 Mar;14(2):183-7
references: 17942517
references: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20896-901
references: 18087043
references: J Clin Neurosci. 2012 Dec;19(12):1689-94
references: 23084347
references: Brain Nerve. 2012 May;64(5):525-35
references: 22570066
references: J Neurosci. 2012 May 9;32(19):6665-9
references: 22573688
references: Nature. 2011 Aug 10;476(7359):214-9
references: 21833088
references: Mult Scler. 2010 Jun;16(6):660-9
references: 20350960
references: J Neurol Neurosurg Psychiatry. 2011 Dec;82(12):1355-9
references: 21622936
references: J Autoimmun. 2012 Feb;38(1):10-9
references: 22123179
references: Brain. 2004 Jul;127(Pt 7):1463-78
references: 15180926
references: Clin Neurol Neurosurg. 2008 Dec;110(10):992-6
references: 18657352
references: Mult Scler. 2011 Mar;17(3):344-52
references: 21149397
references: Curr Top Dev Biol. 2005;68:149-81
references: 16124999
references: PLoS One. 2008 Jul 02;3(7):e2559
references: 18596942
references: Mult Scler. 1998 Jun;4(3):127-31
references: 9762660
references: J Neurol. 2005 May;252(5):526-33
references: 15895275
references: N Engl J Med. 2007 Jan 25;356(4):371-8
references: 17251533
references: Ann Neurol. 2011 Nov;70(5):751-63
references: 22162058
references: Neurology. 2002 Nov 12;59(9):1412-20
references: 12427893
references: N Engl J Med. 2003 Jul 10;349(2):139-45
references: 12853586
references: Immunobiology. 2011 Sep;216(9):979-87
references: 21601937
references: Prog Neuropsychopharmacol Biol Psychiatry. 2003 Aug;27(5):835-9
references: 12921917
references: Neurology. 2009 Dec 8;73(23):2003-10
references: 19996075
references: J Neuroimmunol. 2011 Jan;230(1-2):173-7
references: 20826008
references: Hum Brain Mapp. 2011 Jun;32(6):846-55
references: 21495114
references: Neurology. 2012 Sep 18;79(12):1198-9
references: 22914829
references: PLoS One. 2009 Nov 05;4(11):e7638
references: 19890384
references: PLoS One. 2011 May 06;6(5):e19138
references: 21573104
references: Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8344-9
references: 23154461
references: J Neuroinflammation. 2011 Nov 17;8:161
references: 22093619
references: Brain. 2004 May;127(Pt 5):1101-7
references: 14998914
references: J Neuroimmunol. 2012 Aug 15;249(1-2):109-11
references: 22633195
references: Neurology. 2004 Oct 26;63(8):1439-45
references: 15505162
references: J Neurol. 2008 Oct;255(10):1508-14
references: 18685917
references: J Neuroimmunol. 2002 Jan;122(1-2):132-9
references: 11777552
references: J Immunol. 2012 Nov 15;189(10):5057-65
references: 23071279
references: J Neurol Sci. 2008 May 15;268(1-2):12-7
references: 18054962
references: J Neurol Neurosurg Psychiatry. 2000 May;68(5):627-32
references: 10766895
references: J Neuroinflammation. 2012 May 16;9:93
references: 22591862
references: Life Sci. 2002 Aug 23;71(14):1703-15
references: 12137916
references: Ann Neurol. 2008 Sep;64(3):255-65
references: 18661561
references: J Neurol Sci. 2005 Jun 15;233(1-2):109-12
references: 15869765
references: Arch Neurol. 1999 May;56(5):555-60
references: 10328250
references: Neurology. 2012 Jul 17;79(3):254-60
references: 22700816
references: Neurology. 2003 Feb 25;60(4):647-51
references: 12601107
references: Clin Immunol. 2011 Apr;139(1):12-20
references: 21310664
references: Am J Hum Genet. 2004 Jan;74(1):160-7
references: 14669136
references: Arch Neurol. 2011 Jul;68(7):913-7
references: 21747031
references: J Neuroimmunol. 2010 Dec 15;229(1-2):180-91
references: 20832870
references: J Neuroimmunol. 2012 Jul 15;248(1-2):53-7
references: 22579051
references: Neurology. 2013 Jan 1;80(1):39-46
references: 23175732
references: Arch Neurol. 2008 May;65(5):633-5
references: 18474739
references: J Int Med Res. 2012;40(4):1483-91
references: 22971500
references: Acta Neurol Scand. 2010 Dec;122(6):409-13
references: 20175758
references: J Neuroinflammation. 2007 Jul 01;4:16
references: 17601341
references: Brain. 2005 May;128(Pt 5):1016-25
references: 15758036
references: Inflammation. 2013 Feb;36(1):35-41
references: 22886309
references: Mult Scler. 2010 Apr;16(4):412-26
references: 20207786
references: Neurologia. 2013 Sep;28(7):408-16
references: 22995526
references: N Engl J Med. 2007 Aug 30;357(9):851-62
references: 17660530
references: BMC Neurol. 2012 Aug 22;12:80
references: 22913733
references: Mult Scler. 2006 Feb;12(1):47-57
references: 16459719
references: Neurology. 2012 Aug 7;79(6):531-7
references: 22573631
references: J Neuropathol Exp Neurol. 2010 Jul;69(7):694-703
references: 20535035
references: Neurology. 1992 Jan;42(1):63-7
references: 1370864
references: Neurology. 2009 Jun 9;72(23):1984-8
references: 19506219
references: Sleep. 2006 Mar;29(3):295-7
references: 16553014
references: Trends Immunol. 2011 Jun;32(6):272-7
references: 21530402
references: J Neuroimmunol. 2003 Mar;136(1-2):46-53
references: 12620642
references: J Neuroimmunol. 2006 Nov;180(1-2):17-28
references: 16945427
references: Int Rev Neurobiol. 2007;79:521-35
references: 17531857
references: Eur J Neurol. 2007 Aug;14(8):907-11
references: 17662013
references: Ann Rheum Dis. 2009 Jan;68(1):63-8
references: 18375536
references: Front Cell Neurosci. 2012 Aug 09;6:33
references: 22907989
references: Neurosci Lett. 2011 Jan 10;487(3):273-7
references: 20970478
references: Neuroimage. 2013 Feb 1;66:103-9
references: 23110887
references: Nature. 2010 Apr 29;464(7293):1351-6
references: 20428171
references: J Neuroimmunol. 2010 Jun;223(1-2):92-9
references: 20381173
references: Brain. 2006 Jun;129(Pt 6):1493-506
references: 16569670
references: Am J Epidemiol. 2007 May 15;165(10):1097-109
references: 17329717
references: Neurology. 2004 Sep 28;63(6):1084-6
references: 15452304
references: Am J Med Genet B Neuropsychiatr Genet. 2008 Jun 5;147B(4):467-72
references: 18081025
references: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5941-6
references: 16585503
references: Mult Scler. 1998 Jun;4(3):138-42
references: 9762663
references: NMR Biomed. 2011 Jun;24(5):536-46
references: 21674655
references: Neuropsychopharmacology. 2011 Feb;36(3):559-68
references: 20944553
references: Clin Dev Immunol. 2010;2010:186813
references: 20613949
references: Biochim Biophys Acta. 2011 Feb;1812(2):252-64
references: 20619340
references: Neuroradiology. 2012 Apr;54(4):287-97
references: 21567135
references: J Neuroimmunol. 2012 Jun 15;247(1-2):25-31
references: 22516472
references: Mult Scler. 2010 Jan;16(1):87-92
references: 20028709
references: Brain. 2009 Jan;132(Pt 1):250-9
references: 19022862
references: Acta Neurol Scand. 2010 Jul;122(1):1-8
references: 20003089
references: J Neurol. 2013 Jan;260(1):221-7
references: 22875099
references: J Neuroimmune Pharmacol. 2011 Sep;6(3):354-61
references: 20872081
references: J Immunol. 2011 Oct 15;187(8):4119-28
references: 21911607
references: Neuropathol Appl Neurobiol. 2013 Apr;39(3):270-83
references: 22524708
references: Genes Immun. 2008 Sep;9(6):570-4
references: 18615093
references: J Exp Med. 2003 Dec 1;198(11):1729-40
references: 14657223