Purpose: Multiple Sclerosis (MS) is a presumed autoimmune chronic inflammatory demyelinating disease of the Central Nervous System (CNS) of unknown etiology. Epidemiological studies suggest that MS pathogenesis could be related to an infection superimposed on a predisposing genetic background. Currently, a growing body of data suggests that C. pneumoniae could cause a brain chronic persistent infection acting as a cofactor in the development of the disease. As an intrathecal oligoclonal antibody response directed against the causative agent is usually present in CNS infections, the aim of this study was to verify the distribution C. pneumoniae-specific CSF-restricted oligoclonal IgG bands (OCB) in MS patients and controls. Materials and methods: We measured by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae IgG in 27 relapsing-remitting (RR), 9 secondary progressive (SP) and 5 primary progressive (PP) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Twenty-one patients with other inflammatory neurological disorders (OIND) and 21 with non-inflammatory neurological disorders (NIND) served as neurological controls. To avoid confounding factors, patients with HIV encephalopathy, Alzheimer’s disease and cerebrovascular diseases were excluded from the study Quantitative intrathecal synthesis of anti-C. pneumoniae IgG was determined by Antibody Specific Index (ASI). In all patients with C. pneumoniae-specific intrathecally produced antibodies, the presence of C. pneumoniae-specific CSF OCB was assessed by affinity-mediated immunoblot (AMI). After checking data for normality, statistical analysis was performed by Mann-Whitney U and Chi-square tests (χ2). Bonferroni correction was used for multiple comparisons. Results: Detectable levels of CSF and serum anti-C. pneumoniae IgG were more frequent in total MS and in OIND than in NIND patients. Accordingly, CSF and serum anti-C. pneumoniae IgG mean levels were higher in total MS and in OIND than in NIND patients. However, no significant differences were found for these variables among the various groups. ASI values suggestive of C. pneumoniae-specific intrathecal IgG synthesis were present in a small proportion of MS (12/41; 29.3%), OIND (7/21; 33.3%) and NIND (1/21; 4.8%) patients and were significantly more represented (p < 0.05) in total MS and in OIND than in NIND and in SP (p < 0.01) and PP MS (p < 0.05) than in RR MS. No additional statistical differences were observed for CSF and serum anti-C. pneumoniae IgG mean concentrations as well as for ASI values among RR, SP and PP MS and between MS patients with and without clinical and MRI evidence of disease activity. Among the patients with intrathecally produced anti-C. pneumoniae IgG, C. pneumoniae-specific CSF-restricted OCB were detected only in 3 SP, 1 PP and 1 RR MS patients. Conclusions: These findings confirm that the presence of an intrathecal humoral immune response to C. pneumoniae 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 oligoclonal 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.

Detection of Chlamydia pneumoniae-specific intrathecal oligoclonal antibody response in a subset of patients with progressive forms of multiple sclerosis

CASTELLAZZI, Massimiliano;SERACENI, Silva;TAMBORINO, Carmine;CULTRERA, Rosario;GRANIERI, Enrico Gavino Giuseppe;CONTINI, Carlo;FAINARDI, Enrico
2008

Abstract

Purpose: Multiple Sclerosis (MS) is a presumed autoimmune chronic inflammatory demyelinating disease of the Central Nervous System (CNS) of unknown etiology. Epidemiological studies suggest that MS pathogenesis could be related to an infection superimposed on a predisposing genetic background. Currently, a growing body of data suggests that C. pneumoniae could cause a brain chronic persistent infection acting as a cofactor in the development of the disease. As an intrathecal oligoclonal antibody response directed against the causative agent is usually present in CNS infections, the aim of this study was to verify the distribution C. pneumoniae-specific CSF-restricted oligoclonal IgG bands (OCB) in MS patients and controls. Materials and methods: We measured by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae IgG in 27 relapsing-remitting (RR), 9 secondary progressive (SP) and 5 primary progressive (PP) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Twenty-one patients with other inflammatory neurological disorders (OIND) and 21 with non-inflammatory neurological disorders (NIND) served as neurological controls. To avoid confounding factors, patients with HIV encephalopathy, Alzheimer’s disease and cerebrovascular diseases were excluded from the study Quantitative intrathecal synthesis of anti-C. pneumoniae IgG was determined by Antibody Specific Index (ASI). In all patients with C. pneumoniae-specific intrathecally produced antibodies, the presence of C. pneumoniae-specific CSF OCB was assessed by affinity-mediated immunoblot (AMI). After checking data for normality, statistical analysis was performed by Mann-Whitney U and Chi-square tests (χ2). Bonferroni correction was used for multiple comparisons. Results: Detectable levels of CSF and serum anti-C. pneumoniae IgG were more frequent in total MS and in OIND than in NIND patients. Accordingly, CSF and serum anti-C. pneumoniae IgG mean levels were higher in total MS and in OIND than in NIND patients. However, no significant differences were found for these variables among the various groups. ASI values suggestive of C. pneumoniae-specific intrathecal IgG synthesis were present in a small proportion of MS (12/41; 29.3%), OIND (7/21; 33.3%) and NIND (1/21; 4.8%) patients and were significantly more represented (p < 0.05) in total MS and in OIND than in NIND and in SP (p < 0.01) and PP MS (p < 0.05) than in RR MS. No additional statistical differences were observed for CSF and serum anti-C. pneumoniae IgG mean concentrations as well as for ASI values among RR, SP and PP MS and between MS patients with and without clinical and MRI evidence of disease activity. Among the patients with intrathecally produced anti-C. pneumoniae IgG, C. pneumoniae-specific CSF-restricted OCB were detected only in 3 SP, 1 PP and 1 RR MS patients. Conclusions: These findings confirm that the presence of an intrathecal humoral immune response to C. pneumoniae 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 oligoclonal 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.
2008
multiple sclerosis; chlamidia pneumoniae; antibody; immune response; autoimmune disease
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1683093
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact