HLA-DR expression and neopterin levels as activity markers in multiple sclerosis

We adopted a new double-immunofluorescence labelling assay on prefixed isolated cerebrospinal fluid (CSF) and peripheral blood mononuclear cells from patients with multiple sclerosis (MS) for class II expression (HLA-DR) on T cells. No accumulation of such cells was demonstrated in MS CSF. In contrast, patients with acute aseptic meningo-encephalitis (AM) displayed accumulation in CSF of activated, DR positive T cells as a marker of actively involved cellular immunity within the CNS. Thus, enumeration of DR expressing T cells in CSF can not currently be used as reflection of disease activity in MS. In contrast, determination of neopterin levels in CSF may be a useful marker of disease activity in this disease. Levels of neopterin, a factor known to be released from macrophages and monocytes at increased rates in cellular immune reactions, were higher in CSF in 10 of 12 patients with MS during clinical exacerbations in comparison with remissions. This significant elevation in CSF was not reflected in serum. We have also reported high neopterin levels in CSF in a majority of patients during acute phase of AM followed by normalization after clinical recovery. It is concluded that neopterin in CSF is a valuable marker of acute cellular immune response, and should represent an objective way to monitor disease activity in MS, e.g. in relation to effects of putative therapeutic agent.