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Gürkov, Robert (2005): Analysis of intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis patients. Dissertation, LMU München: Faculty of Medicine
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Abstract

Multiple Sclerosis (MS) is one of the most frequent organic diseases of the nervous system, with a prevalence of 30-60 per 100,000 inhabitans. It is charcterized by an inflammatory destruction of the myelin sheaths in the white matter of the central nervous system, which may lead to severe disability and death. The underlying mechanism has not been clearly elucidated yet, but involves an attack of the body’s immune system against some of its own neural tissue antigens. One of the immunopathologic hallmarks of MS is the chronic intrathecal production of immunoglobulin (Ig). This contains IgG of very restricted variability, i.e. oligoclonal IgG, and in addition, recognizes a panel of different pathogens such as measles, rubella, and herpes zoster virus. While the antigen-specificity of the largest part of oligoclonal IgG in multiple sclerosis is unknown, the oligoclonal IgG arising during CNS infections are reactive against the specific pathogen. Recently, a link between Chlamydia (C.) pneumoniae and multiple sclerosis has been claimed. To test the possible role of C. pneumoniae in multiple sclerosis, we analyzed a) whether there is intrathecal IgG production against C. pneumoniae in multiple sclerosis and b) whether the oligoclonal IgG in the CSF of multiple sclerosis patients recognize C. pneumoniae. By studying paired serum/CSF samples from 120 subjects (definite multiple sclerosis: 46; probable multiple sclerosis: 12; OIND: 35; OND: 27) by ELISA, we found that 24% of all patients with definite multiple sclerosis, but only 5% of patients with other inflammatory or non-inflammatory diseases produced IgG specific for C. pneumoniae intrathecally (definite multiple sclerosis versus OIND: p = 0.027). The presence of intrathecal IgG to C. pneumoniae was independent of the duration of disease and relatively stable over time. The major CSF oligoclonal IgG bands from multiple sclerosis-patients with an intrathecal Ig-production to C. pneumoniae did not react to C. pneumoniae by IEF-Western as seen by isolectric focusing and subsequent affinity-mediated immunoblot (IEF-Western) towards purified elementary bodies and reticulate bodies of C. pneumoniae. By contrast, the IgG in the CSF of control patients with neuroborreliosis strongly reacted with their specific pathogen, Borrelia burgdorferi by IEF-Western. Concomitant analysis of the CSF of 23 patients with a nested PCR for C. pneumoniae was negative in all cases. Together, these findings strongly suggest that the immune response to C. pneumoniae is part of a polyspecific intrathecal Ig production, as is commonly observed with other pathogens. This argues against a specific role of C. pneumoniae in multiple sclerosis.