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Research Article| Volume 217, ISSUE 2, P181-188, February 15, 2004

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Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms

  • Enrico Fainardi
    Correspondence
    Corresponding author. Department of Neurology, Section of Neurology, University of Ferrara, Corso della Giovecca 203, Ferrara I-44100, Italy. Tel.: +39-532-236304; fax: +39-532-205525.
    Affiliations
    Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

    Section of Neuroradiology, Department of Neurosciences, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy
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  • Massimiliano Castellazzi
    Affiliations
    Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy
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  • Ilaria Casetta
    Affiliations
    Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy
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  • Rosario Cultrera
    Affiliations
    Section of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Ferrara, via Fossato di Mortara, 23, Ferrara I-44100, Italy
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  • Luca Vaghi
    Affiliations
    Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy
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  • Enrico Granieri
    Affiliations
    Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy
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  • Carlo Contini
    Affiliations
    Section of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Ferrara, via Fossato di Mortara, 23, Ferrara I-44100, Italy
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      Abstract

      The purpose of this study was to provide further insight into the effective relevance of the association between Chlamydia pneumoniae and MS. We evaluated by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae IgG in 46 relapsing–remitting (RR), 14 secondary progressive (SP) and 11 primary progressive (PP) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Fifty-one patients with other inflammatory neurological disorders (OIND) and 52 with non-inflammatory neurological disorders (NIND) were used as controls. A C. pneumoniae-specific intrathecal IgG synthesis as detected by the relative specific index was present in a small proportion of MS (17%), OIND (22%) and NIND (2%) patients and was significantly more frequent in MS and in OIND than in NIND (p<0.001) and in SP and PP MS than in RR MS patients (p<0.02). Among the patients with C. pneumoniae-specific intratecally produced antibodies, CSF high-affinity anti-C. pneumoniae IgG were found in the majority of SP or PP MS, occasionally in OIND, but not in RR MS and NIND patients. These findings confirm that the presence of a humoral immune response to C. pneumoniae within the central nervous system (CNS) is not selectively restricted to MS, but is shared by several inflammatory neurological conditions. In addition, our results suggest that an intrathecal production of C. pneumoniae-specific high-affinity IgG can occur in a subset of patients with MS progressive forms in which a C. pneumoniae brain chronic persistent infection may play an important pathogenetic role.

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      References

        • Noseworthy J.H.
        • Lucchinetti C.
        • Rodriguez M.
        • Weinshenker B.G.
        Multiple sclerosis.
        N. Engl. J. Med. 2000; 343: 938-952
        • Meinl E.
        Concepts of viral pathogenesis of multiple sclerosis.
        Curr. Opin. Neurol. 1999; 12: 303-307
        • Yucesan C.
        • Sriram S.
        Chlamydia pneumoniae infection of the central nervous system.
        Curr. Opin. Neurol. 2001; 14: 355-359
        • Sriram S.
        • Stratton C.W.
        • Yao S.Y.
        • Tharp A.
        • Ding L.
        • Bannan J.D.
        • et al.
        Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis.
        Ann. Neurol. 1999; 46: 6-14
        • Layh-Schmitt G.
        • Bend C.
        • Hildt U.
        • Dong-Si T.
        • Jüttler E.
        • Schnitzler P.
        • et al.
        Evidence for infection with Chlamydia pneumoniae in a subgroup of patients with multiple sclerosis.
        Ann. Neurol. 2000; 47: 652-655
        • Treib J.
        • Haaß A.
        • Stille W.
        • Maass M.
        • Stephan C.
        • Holzer G.
        • et al.
        Multiple sclerosis and Chlamydia pneumoniae.
        Ann. Neurol. 2000; 47: 408
        • Ikejima H.
        • Haranaga S.
        • Takemura H.
        • Kamo T.
        • Takahashi Y.
        • Friedman H.
        • et al.
        PCR-based method for isolation and detection of Chlamydia pneumoniae DNA in cerebrospinal fluid.
        Clin. Diagn. Lab. Immunol. 2001; 8: 499-502
        • Gieffers J.
        • Poh D.
        • Treib J.
        • Dittmann R.
        • Stephan C.
        • Klotz K.
        • et al.
        Presence of Chlamydia pneumoniae DNA in the cerebral spinal fluid is a common phenomenon in a variety of neurological diseases and not restricted to multiple sclerosis.
        Ann. Neurol. 2001; 49: 585-589
        • Hao Q.
        • Miyashita N.
        • Matsui M.
        • Wang H.Y.
        • Matsushima T.
        • Saida T.
        Chlamydia pneumoniae infection associated with enhanced MRI spinal lesions in multiple sclerosis.
        Mult. Scler. 2002; 8: 436-440
        • Boman J.
        • Roblin P.M.
        • Sundström P.
        • Sandström M.
        • Hammerschlag M.R.
        Failure to detect Chlamydia pneumoniae in the central nervous system of patients with MS.
        Neurology. 2000; 54: 265
        • Pucci E.
        • Taus C.
        • Carthechini E.
        • Morelli M.
        • Giuliani G.
        • Clementi M.
        • et al.
        Lack of Chlamydia infection of the central nervous system in multiple sclerosis.
        Ann. Neurol. 2000; 48: 340-399
        • Saiz A.
        • Marcos M.A.
        • Graus F.
        • Vidal J.
        • Jimenez de Anta M.T.
        No evidence of CNS infection with Chlamydia pneumoniae in patients with multiple sclerosis.
        J. Neurol. 2001; 248: 617-618
        • Derfuss T.
        • Gürkov R.
        • Bergh F.T.
        • Goebels N.
        • Hartmann M.
        • Barz C.
        • et al.
        Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response.
        Brain. 2001; 124: 1325-1335
        • Hammerschlag M.R.
        • Ke Z.
        • Lu F.
        • Roblin P.
        • Boman J.
        • Kalman B.
        Is Chlamydia pneumoniae present in brain lesions of patients with multiple sclerosis?.
        J. Clin. Microbiol. 2000; 38: 4274-4276
        • Morré S.A.
        • De Groot C.J.A.
        • Killestein J.
        • Meijer C.J.L.M.
        • Polman C.H.
        • Van der Valk P.
        • et al.
        Is Chlamydia pneumoniae present in the central nervous system of multiple sclerosis patients?.
        Ann. Neurol. 2000; 48: 399
        • Lenz D.C.
        • Lu L.
        • Conant S.B.
        • Wolf N.A.
        • Gérard H.C.
        • Whittum-Hudson J.A.
        • et al.
        A Chlamydia pneumoniae-specific peptide induces experimental autoimmune encephalomyelitis in rats.
        J. Immunol. 2001; 167: 1803-1808
        • Krametter D.
        • Niederwieser G.
        • Berghold A.
        • Birnbaum G.
        • Strasser-Fuchs S.
        • Hartung H.P.
        • et al.
        Chlamydia pneumoniae in multiple sclerosis: humoral immune responses in serum and cerebrospinal fluid and correlation with disease activity marker.
        Mult. Scler. 2001; 7: 13-18
        • Yao S.Y.
        • Stratton C.W.
        • Mitchell W.M.
        • Sriram S.
        CSF oligoclonal bands in MS include antibodies against Chlamydiophila antigens.
        Neurology. 2001; 56: 1168-1176
        • Sindic C.J.M.
        • Monteyne P.
        • Laterre E.C.
        The intrathecal synthesis of virus-specific oligoclonal IgG in multiple sclerosis.
        J. Neuroimmunol. 1994; 54: 75-80
        • Conrad A.J.
        • Chiang E.Y.
        • Andeen L.E.
        • Avolio C.
        • Walker S.M.
        • Baumhefner R.W.
        • et al.
        Quantitation of intrathecal measles virus IgG antibody synthesis rate: subacute sclerosing panencephalitis and multiple sclerosis.
        J. Neuroimmunol. 1994; 54: 99-108
        • Luxton R.W.
        • Zeman A.
        • Holzel H.
        • Harvey P.
        • Wilson J.
        • Kocen R.
        • et al.
        Affinity of antigen-specific IgG distinguishes multiple sclerosis from encephalitis.
        J. Neurol. Sci. 1995; 132: 11-19
        • Reiber H.
        • Ungefehr S.
        • Jacobi C.
        The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis.
        Mult. Scler. 1998; 4: 111-117
        • Poser C.M.
        • Paty D.W.
        • Scheimberger L.
        • McDonald W.I.
        • Davis F.A.
        • Ebers G.C.
        • et al.
        New diagnostic criteria for MS: guidelines for research protocols.
        Ann. Neurol. 1983; 13: 227-231
        • Lublin D.F.
        • Reingold S.C.
        Defining the clinical course of multiple sclerosis: results of an international survey.
        Neurology. 1996; 46: 907-911
        • Kurtzke J.F.
        Rating neurological impairment in multiple sclerosis: an expanded disability scale (EDSS).
        Neurology. 1983; 33: 1444-1452
        • Salden H.J.M.
        • Bas B.M.
        • Hermas J.T.H.
        • Janson P.C.V.
        Analytical performance of three commercially available nephelomethers compared quantifying protein in serum and cerebrospinal fluid.
        Clin. Chem. 1988; 34: 1594-1596
        • Tibbling G.
        • Link H.
        • Öhman S.
        Principles of albumin and IgG analyses in neurological disorders: I. Establishment of reference value.
        Scand. J. Clin. Lab. Invest. 1977; 37: 385-390
        • Contini C.
        • Fainardi E.
        • Seraceni S.
        • Granieri E.
        • Castellazzi M.
        • Cultrera R.
        Molecular identification and antibody testing of Chlamydiophila pneumoniae in a subgroup of patients with HIV-associated dementia complex preliminary results.
        J. Neuroimmunol. 2003; 136: 172-177
        • Reiber H.
        • Lange P.
        Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain.
        Clin. Chem. 1991; 37: 1153-1160
        • Reiber H.
        • Felgenhauer K.
        Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system.
        Clin. Chem. Acta. 1987; 163: 319-328
        • Reiber H.
        Evaluation of blood cerebrospinal fluid barrier function and quantification of the humoral immune response within the central nervous system.
        in: Thompson E.J. Trojano M. Livrea P. Cerebrospinal fluid analysis in multiple sclerosis. Springer, Milano1996: 51-72
        • Sotgiu S.
        • Piana A.
        • Pugliatti M.
        • Sotgiu A.
        • Deiana G.A.
        • Sgaramella E.
        • et al.
        Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis and neurological controls.
        Mult. Scler. 2001; 7: 371-374
        • Thompson A.J.
        • Polman C.H.
        • Miller D.H.
        • Mc Donald W.I.
        • Brochet B.
        • Filippi M.
        • et al.
        Primary progressive multiple sclerosis.
        Brain. 1997; 120: 1085-1096
        • McDonnell G.V.
        • Hawkins S.A.
        Primary progressive multiple sclerosis: increasing clarity but many unanswered questions.
        J. Neurol. Sci. 2002; 199: 1-15
        • Hafler D.A.
        The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis.
        J. Clin. Invest. 1999; 104: 527-529
        • Luxton R.W.
        • Thompson E.J.
        Affinity distribution of antigen-specific IgG in patients with multiple sclerosis and in patients with viral encephalitis.
        J. Immunol. Methods. 1990; 131: 277-282