Analysis of intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis patients

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.