Clues to the immunopathogenesis of multiple sclerosis by investigating untreated patients during the very early stage of disease |
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Authors: | M Söderström |
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Institution: | (1) Department of Ophthalmology and Neuroimmunology Unit, Division of Neurology, Huddinge University Hospital, Huddinge, Sweden and Karolinska Institute, S-14186 Stockholm, Sweden, SE |
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Abstract: | Plethora of abnormalities of the immune system has been described in multiple sclerosis (MS). They include a number of myelin
antigens (e. g. MBP, MOG, PLP, MAG), the presence of reactive T cells in blood and, further enriched, in the cerebrospinal
fluid (CSF), large numbers of B cells in the CSF secreting antibodies of multiple but unknown specificities, an increase of
mononuclear cells (MNC) expressing and secreting both pro- and anti-inflammatory cytokines, including Th1 cytokines interferon-gamma
(IFN-γ) and interleukin (IL)-6, the Th2 related IL-4 and IL-10, and the Th3-driven TGF-β, elevated numbers of MNC in both
blood and CSF expressing a spectrum of metalloproteinases and their inhibitors, as well as many other aberrations. However,
no consistent patterns have emerged that relate any of these findings to clinical variables such as exacerbations, during
of disease, disability, or lesions in the central nervous system (CNS) detected at magnetic resonance imaging. In order to
elucidate the relevance of these immunological abnormalities in the pathogenesis of MS, my colleagues and I studied patients
with acute monosymptomatic optic neuritis (ON) and compared them with patients with clinically definite MS (CDMS). The patients
have not been treated and have not received corticosteroids or interferon-β. When comparing these two groups, we were unable
to identify any differences in any of the variables mentioned. Thus, very early MS, as represented by ON, shows the same full-blown
pattern of immunological abnormalities seen in CDMS. Furthermore, a complete epitope spread affecting MBP, MOG, PLP, MAG and
other myelin components is already present in ON. Whether any of these alterations play a pathogenetic role is still unsettled. |
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Keywords: | Multiple sclerosis Optic neuritis Cytokines |
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