• the presence of C. pneumoniae gene sequences in the cerebrospinal fluid of patients who have the disease, and culture of the organism when sensitive cultural methods are used [Sriram S, Stratton CW, Yao S, Tharp A, Ding L, Bannan JD, Mitchell WM. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann Neurol. 1999 Jul;46(1):6-14.] • an association of new C. pneumoniae respiratory infections with episodes of clinical relapse [Buljevac D, Verkooyen RP, Jacobs BC, Hop W, van der Zwaan LA, van Doorn PA, Hintzen RQ. Chlamydia pneumoniae and the risk for exacerbation in multiple sclerosis patients. Ann Neurol. 2003 Dec;54(6):828-31.] • a statistically significant elevation of C. pneumoniae-specific serum antibody levels when the disease shifts into the progressive form [Munger KL, Peeling RW, Hernán MA, Chasan-Taber L, Olek MJ, Hankinson SE, Hunter D, Ascherio A. Infection with Chlamydia pneumoniae and risk of multiple sclerosis. Epidemiology 2003 14:2 141-147] • antibodies to C. pneumoniae in the cerebrospinal fluid of patients with the disease [(1.) Yao, S., Stratton, C.W., Mitchell, W.M., Sriram, S. (2001). CSF oligoclonal bands in multiple sclerosis represent antibodies against Chlamydophila. Neurology 56, 1168-76. (2.) Fainardi, E., Castellazzi, M., Casetta, I. et al. (2004). Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated with a subset of multiple sclerosis patients with progressive forms. Journal of the Neurological Sciences 217, 181-8.] • evidence of active C. pneumoniae protein synthesis in the central nervous system, with production of a bacterial protein evoking an antibody shown to cause death of oligodendrocyte precursor cells [Cid C, Alvarez-Cermeno JC, Camafeita E, Salinas M, Alcazar A. Antibodies reactive to heat shock protein 90 induce oligodendrocyte precursor cell death in culture. Implications for demyelination in multiple sclerosis. FASEB J. 2004 Feb;18(2):409-11.] •a peptide specific to C. pneumoniae causes inflammatory CNS disease (with some parallels to MS) in rats [Lenz DC, Lu L, Conant SB, Wolf NA, Gerard HC, Whittum-Hudson JA, Hudson AP, Swanborg RH. A Chlamydia pneumoniae-specific peptide induces experimental autoimmune encephalomyelitis in rats. J Immunol. 2001 Aug 1;167(3):1803-8.] •C. pneumoniae gene transcription in the CSF of patients with MS [Dong-Si T, Weber J, Liu YB, Buhmann C, Bauer H, Bendl C, Schnitzler P, Grond-Ginsbach C, Grau AJ. Increased prevalence of and gene transcription by Chlamydia pneumoniae in cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis. J Neurol. 2004 May;251(5):542-547.] • MRI improvement in antibiotic-treated patients with early disease in a small but fastidious double-blind trial of non-immunomodulatory antibiotics [Sriram S, Yao SY, Stratton C, Moses H, Narayana PA, Wolinsky JS. Pilot study to examine the effect of antibiotic therapy on MRI outcomes in RRMS. J Neurol Sci. 2005 Jul 15;234(1-2):87-91.]
• MRI improvement, with reduction of the number of Gd-enhancing lesions, in a second treatment study with minocycline [Metz LM, Zhang Y, Yeung M, Patry DG, Bell RB, Stoian CA, et al. Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol. 2004 May;55(5):756.]
• An association of C. pneumoniae in the CNS with MS is demonstrated by immunohistochemical, molecular and ultrastructural methods. [Sriram S, Ljunggren-Rose A, Yao SY, Whetsell WO Jr. Detection of chlamydial bodies and antigens in the central nervous system of patients with multiple sclerosis. J Infect Dis. 2005;192(7):1219-28.]
• C. pneumoniae occurs in a persistent and metabolically active state in the CSF and peripheral blood monocytes of persons with active MS [Chlamydophila pneumoniae DNA and mRNA transcript levels in peripheral blood mononuclear cells and cerebrospinal fluid of patients with multiple sclerosis. Contini C, Seraceni S, Castellazzi M, Granieri E, Fainardi E. Neurosci Res. 2008 Sep;62(1):58-61.]
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