title: Comparison of DNA-hydrolyzing antibodies from the cerebrospinal fluid and serum of patients with multiple sclerosis.
abstract: It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Division, Novosibirsk, Russia.
authors.forename: Taisiya A
authors.initials: TA
authors.lastname: Parkhomenko
authors.affiliation: Novosibirsk Medical University, Ministry of Public Health of Russian Federation, Novosibirsk, Russia.
authors.forename: Vasilii B
authors.initials: VB
authors.lastname: Doronin
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, Ferrara University, Ferrara, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Castellazzi
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, Ferrara University, Ferrara, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Padroni
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, Ferrara University, Ferrara, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Pastore
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Division, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Buneva
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, Ferrara University, Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Granieri
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Division, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.
authors.forename: Georgy A
authors.initials: GA
authors.lastname: Nevinsky
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology; D017151:Antibodies, Catalytic / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D017151:Antibodies, Catalytic; D007074:Immunoglobulin G; D004247:DNA
references.citation: J Biotechnol. 1998 Apr 15;61(2):109-15
references.pmid: 9654744
references.citation: J Clin Immunol. 2001 Mar;21(2):81-92
references.pmid: 11332657
references.citation: Science. 1995 Sep 29;269(5232):1835-42
references.pmid: 7569920
references.citation: Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8876-80
references.pmid: 8415624
references.citation: J Mol Recognit. 2010 Sep-Oct;23(5):486-94
references.pmid: 20119969
references.citation: Immunol Lett. 2003 May 1;86(3):291-7
references.pmid: 12706534
references.citation: J Cell Mol Med. 2010 Mar;14(3):699-709
references.pmid: 19438809
references.citation: Genes Immun. 2003 Mar;4(2):138-46
references.pmid: 12618862
references.citation: Immunol Lett. 2006 Feb 28;103(1):75-81
references.pmid: 16310860
references.citation: J Cell Mol Med. 2004 Jul-Sep;8(3):359-68
references.pmid: 15491511
references.citation: J Neurol. 1993 Jul;240(7):417-22
references.pmid: 8410082
references.citation: Nat Immunol. 2001 Sep;2(9):762-4
references.pmid: 11526378
references.citation: Science. 1992 May 1;256(5057):665-7
references.pmid: 1585181
references.citation: Curr Opin Neurol. 1999 Jun;12(3):303-7
references.pmid: 10499175
references.citation: J Neurol Sci. 2004 Feb 15;217(2):181-8
references.pmid: 14706222
references.citation: Science. 1989 Jun 9;244(4909):1158-62
references.pmid: 2727702
references.citation: Trends Cell Biol. 1999 Dec;9(12):M24-8
references.pmid: 10611676
references.citation: Immunol Lett. 2001 Apr 2;76(3):163-7
references.pmid: 11306143
references.citation: Ann Neurol. 1996 Feb;39(2):233-40
references.pmid: 8967755
references.citation: J Immunol. 2008 Jan 15;180(2):1258-67
references.pmid: 18178866
references.citation: Mol Biol (Mosk). 1995 Jul-Aug;29(4):727-49
references.pmid: 7476940
references.citation: Appl Biochem Biotechnol. 1994 May-Jun;47(2-3):229-37; discussion 237-9
references.pmid: 7944340
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):281-6
references.pmid: 16387849
references.citation: FEBS Lett. 2006 Sep 18;580(21):5089-95
references.pmid: 16950261
references.citation: Appl Biochem Biotechnol. 1998 Oct;75(1):3-12
references.pmid: 10214693
references.citation: Neurology. 1996 Apr;46(4):907-11
references.pmid: 8780061
references.citation: Med Sci Monit. 2005 Aug;11(8):BR266-72
references.pmid: 16049372
references.citation: J Cell Mol Med. 2007 May-Jun;11(3):531-51
references.pmid: 17635644
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1793-8
references.pmid: 11172030
references.citation: Proc Natl Acad Sci U S A. 1990 Nov;87(21):8341-4
references.pmid: 2236044
references.citation: Neurology. 1983 Nov;33(11):1444-52
references.pmid: 6685237
references.citation: J Cell Mol Med. 2003 Jul-Sep;7(3):265-76
references.pmid: 14594551
references.citation: Ann Neurol. 2001 Jul;50(1):121-7
references.pmid: 11456302
references.citation: Appl Biochem Biotechnol. 1998 Oct;75(1):45-61
references.pmid: 10214696
references.citation: Clin Chem. 1988 Aug;34(8):1594-6
references.pmid: 3402061
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13526-31
references.pmid: 11095704
references.citation: Int Rev Immunol. 1993;10(2-3):229-40
references.pmid: 8360587
references.citation: EXS. 1995;73:121-38
references.pmid: 7579971