title: Infectious causes of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a serious chronic neurological disorder in which demyelination and inflammation occur in the white matter of the CNS. The findings of many epidemiological studies and a discordance of MS in monozygotic twins suggest that the disorder is acquired. The most likely cause is a virus because more than 90% of patients with MS have high concentrations of IgG, manifest as oligoclonal bands, in the brain and CSF. Most chronic inflammatory CNS disorders are infectious. More indirect evidence that MS is caused by a virus is the association of several viruses with demyelinating encephalomyelitis in human beings, and the induction of demyelination in animals infected with viruses in research. Nevertheless, no virus has been isolated from the brains of patients who had MS. Molecular analysis of IgG gene specificity in the brain and CSF of those with MS has shown features of an antigen-driven response: clonal amplification and extensive somatic mutations. A viral antigen against which the IgG in MS brain and CSF is directed might be identified.
authors.affiliation: Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. don.gilden@uchsc.edu <don.gilden@uchsc.edu>
authors.forename: Donald H
authors.initials: DH
authors.lastname: Gilden
mesh_terms: D000818:Animals; D023521:Chlamydophila Infections / Q000150:complications; D016993:Chlamydophila pneumoniae; D006801:Humans; D007239:Infections / Q000150:complications*; D009103:Multiple Sclerosis / Q000382:microbiology* / Q000821:virology; D014777:Virus Diseases / Q000150:complications
references.citation: Acta Neuropathol. 2001 Jun;101(6):601-4
references.pmid: 11515789
references.citation: Cold Spring Harb Symp Quant Biol. 1975;39 Pt 2:913-8
references.pmid: 169046
references.citation: Lancet. 1977 Sep 24;2(8039):637-9
references.pmid: 71451
references.citation: N Engl J Med. 1969 Sep 11;281(11):585-9
references.pmid: 4980073
references.citation: J Neurol. 1990 Oct;237(6):352-5
references.pmid: 2277268
references.citation: J Neurol Neurosurg Psychiatry. 1994 Aug;57(8):975-6
references.pmid: 7520057
references.citation: Infect Immun. 1979 Sep;25(3):1008-15
references.pmid: 227786
references.citation: Acta Neurol Scand Suppl. 1997;169:38-44
references.pmid: 9174639
references.citation: Science. 1989 Apr 21;244(4902):359-62
references.pmid: 2523562
references.citation: Acta Neurol Scand. 1993 May;87(5):353-5
references.pmid: 8392772
references.citation: Lab Invest. 1977 Dec;37(6):595-602
references.pmid: 202801
references.citation: Neurology. 1999 Oct 12;53(6):1367-8
references.pmid: 10522909
references.citation: N Engl J Med. 1978 May 11;298(19):1068-9
references.pmid: 205790
references.citation: Neurology. 1992 Sep;42(9):1798-804
references.pmid: 1381067
references.citation: Arch Neurol. 2002 Jun;59(6):929-33
references.pmid: 12056928
references.citation: Virology. 1992 Nov;191(1):502-5
references.pmid: 1413524
references.citation: J Infect Dis. 2003 May 1;187(9):1377-87
references.pmid: 12717618
references.citation: Ann Neurol. 1991 Mar;29(3):333-6
references.pmid: 2042949
references.citation: JAMA. 2001 Dec 26;286(24):3083-8
references.pmid: 11754673
references.citation: Lancet. 1967 Mar 11;1(7489):542-4
references.pmid: 4163906
references.citation: Eur J Neurol. 2002 Jul;9(4):329-41
references.pmid: 12099914
references.citation: Neurology. 2000 Jul 25;55(2):178-84
references.pmid: 10908887
references.citation: Rev Clin Esp. 2002 Nov;202(11):588-91
references.pmid: 12392645
references.citation: Science. 1976 Apr 2;192(4234):62-4
references.pmid: 176726
references.citation: J Virol. 2003 Apr;77(7):4383-8
references.pmid: 12634394
references.citation: Hybrid Hybridomics. 2002 Apr;21(2):93-7
references.pmid: 12031097
references.citation: Nat Med. 1997 Dec;3(12):1394-7
references.pmid: 9396611
references.citation: J Immunol. 2003 Sep 1;171(5):2725-33
references.pmid: 12928426
references.citation: Ann Neurol. 2004 Apr;55(4):458-68
references.pmid: 15048884
references.citation: J Med Virol. 2001 Jan;63(1):45-51
references.pmid: 11130886
references.citation: J Neuropathol Exp Neurol. 1976 May;35(3):259-70
references.pmid: 178834
references.citation: Epidemiol Rev. 1982;4:45-65
references.pmid: 6754409
references.citation: Ann Neurol. 2004 Jul;56(1):97-107
references.pmid: 15236406
references.citation: Epidemiology. 2000 Mar;11(2):220-4
references.pmid: 11021623
references.citation: Ann Neurol. 1996 Nov;40(5):805-9
references.pmid: 8957025
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7583-8
references.pmid: 9207135
references.citation: J Neurovirol. 2000 May;6 Suppl 2:S101-8
references.pmid: 10871796
references.citation: Neurology. 1991 Mar;41(3):335-43
references.pmid: 1848687
references.citation: J Neurovirol. 1995 Sep;1(3-4):253-8
references.pmid: 9222363
references.citation: Ann Neurol. 1992 May;31(5):525-33
references.pmid: 1596089
references.citation: Brain. 2000 May;123 ( Pt 5):968-74
references.pmid: 10775541
references.citation: Scand J Immunol. 1976;5(8):979-92
references.pmid: 996452
references.citation: Mult Scler. 1998 Apr;4(2):49-54
references.pmid: 9599333
references.citation: Lancet Neurol. 2004 Feb;3(2):104-10
references.pmid: 14747002
references.citation: Lancet. 1971 Jun 19;1(7712):1257-60
references.pmid: 4104715
references.citation: Neurology. 2000 Mar 28;54(6):1227-32
references.pmid: 10746589
references.citation: Mult Scler. 1999 Oct;5(5):355-62
references.pmid: 10516780
references.citation: Curr Opin Microbiol. 1999 Aug;2(4):398-402
references.pmid: 10458992
references.citation: Ann Neurol. 1979 Jan;5(1):89-94
references.pmid: 570821
references.citation: J Neurovirol. 2002 Jun;8(3):250-6
references.pmid: 12053279
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12877-82
references.pmid: 14569025
references.citation: J Neurovirol. 1999 Apr;5(2):134-9
references.pmid: 10321977
references.citation: Acta Neurol Scand. 1998 Nov;98(5):302-9
references.pmid: 9858098
references.citation: Ann Neurol. 1998 Feb;43(2):236-43
references.pmid: 9485065
references.citation: Am J Epidemiol. 1978 Jun;107(6):451-61
references.pmid: 665660
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7440-4
references.pmid: 7638210
references.citation: Trends Microbiol. 2001 Apr;9(4):152-4
references.pmid: 11286864
references.citation: JAMA. 2003 Mar 26;289(12):1533-6
references.pmid: 12672770
references.citation: J Neurol Neurosurg Psychiatry. 2002 Oct;73(4):439-43
references.pmid: 12235316
references.citation: Brain. 2002 Jan;125(Pt 1):159-65
references.pmid: 11834601
references.citation: Acta Neurol Scand. 2004 Apr;109(4):270-5
references.pmid: 15016009
references.citation: J Clin Virol. 2000 May;16(3):159-78
references.pmid: 10738136
references.citation: Lancet. 1977 Jun 11;1(8024):1262
references.pmid: 68362
references.citation: Ann Neurol. 1999 Jul;46(1):6-14
references.pmid: 10401775
references.citation: Infection. 2002 Jun;30(3):145-9
references.pmid: 12120939
references.citation: J Immunol. 2004 Jul 1;173(1):649-56
references.pmid: 15210828
references.citation: Mult Scler. 1996 Feb;1(4):193-9
references.pmid: 9345433
references.citation: Acta Neurol Scand Suppl. 1997;169:76-8
references.pmid: 9174642
references.citation: Ann Neurol. 1979 Jan;5(1):6-21
references.pmid: 371519
references.citation: Mult Scler. 1996 Nov;2(4):179-83
references.pmid: 9345371
references.citation: Lancet. 1972 Jul 1;2(7766):1-5
references.pmid: 4113621
references.citation: Ann Intern Med. 1950 Aug;33(2):298-320
references.pmid: 15433121
references.citation: Acta Neurol Scand. 1991 Dec;84(6):507-13
references.pmid: 1724334
references.citation: Brain Res. 1971 May 21;28(3):365-90
references.pmid: 4939243
references.citation: Lancet Neurol. 2004 Dec;3(12):709-18
references.pmid: 15556803
references.citation: Mult Scler. 2001 Feb;7(1):13-8
references.pmid: 11321187
references.citation: J Neuroimmunol. 1998 Jun 15;86(2):213-7
references.pmid: 9663568