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Cerebrospinal fluid molecular demonstration of Chlamydia pneumoniae DNA is associated to clinical and brain magnetic resonance imaging activity in a subset of patients with relapsing-remitting multiple sclerosis

Section of Infectious Diseases, Department of Clinical & Experimental Medicine, University of Ferrara, via Fossato di Mortara, 23, I-44100 Ferrara, Italy, cnc{at}dns.unife.it

R Cultrera

Section of Infectious Diseases, Department of Clinical & Experimental Medicine, University of Ferrara, via Fossato di Mortara, 23, I-44100 Ferrara, Italy

S Seraceni

Section of Infectious Diseases, Department of Clinical & Experimental Medicine, University of Ferrara, via Fossato di Mortara, 23, I-44100 Ferrara, Italy

M Castellazzi

Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

E Granieri

Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

E Fainardi

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

To further explore the link between Chlamydia pneumoniae and multiple sclerosis (MS), we examined cerebrospinal fluid (CSF) samples from 71 patients with MS and from 72 patients suffering from other inflammatory neurological disorders (OIND) or noninflammatory neurological disorders (NIND). All samples were analysed by a touchdown nested polymerase chain reaction (n-PCR) forC. pneumoniae with primer sets which amplify target sequence genes encoding the major outer membrane protein (MOMP), the16S rRNA and the Hsp- 70 protein. A molecular study was also performed to evaluate genetic diversity among isolates of C. pneumoniae and to compare chlamydial sequences. PCR was found positive in 36.6% of total MS, in 28.1% of OIND and in 37.5% of NIND patients, without any statistical differences among the various groups examined. CSF PCR evidence of C. pneumoniae was significantly more frequent in relapsing-remitting (RR) than in secondary progressive (SP) (PB-0.001) and in primary progressive (PP)MS (PB-0.05), in clinically active than in clinically stable MS (PB-0.05) and in MRI active than in MRI inactive MS(PB-0.001). The analysis of CSF expression of each single C. pneumoniae-specific gene revealed that detectable levels of MOMP were significantly more frequent in MS patients with relapse (PB-0.05), whereas PCR positivity for MOMP and 16S rRNA genes were more represented in MS patients with clinical and MRI evidence of disease activity (PB-0.05). Similar rates for MOMP and 16S rRNA genes were detected in CSF of both MS patients and controls, whereas CSF PCR positivity for Hsp-70 gene was observed in only three active RR MS patients. Sequence analysis revealed significant homologies withC. pneumoniae compared to otherChlamydial spp. These findings confirm that theC. pneumoniae detection within the central nervous system (CNS) is not selectively restricted to MS, but accounts in a variety of neurological diseases. In addition, our results suggest that CSF C. pneumoniae-specific DNA detection can occur in a subset of MS patients with clinical and MRI active RR form in whom a C. pneumoniae brain chronic persistent infection may play a significant role in the development of disease.

Key Words: cerebrospinal fluid • Chlamydia pneumoniae • magnetic resonance imaging • multiple sclerosis • polymerase chain reaction

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