Clues to the immunopathogenesis of multiple sclerosis by investigating untreated patients during the very early stage of disease.

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-gamma) and interleukin (IL)-6, the Th2 related IL-4 and IL-10, and the Th3-driven TGF-beta, 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, duration 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-beta. 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.