Abstract
It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.
Highlights
Multiple sclerosis (MS) is a chronic demyelinating pathology of the central nervous system presenting a serious medical and social problem
First we measured a relative concentration of total protein in cerebrospinal fluid (CSF) and sera of MS patients (Table 2)
The relative concentrations of total protein of CSFs and sera (47–74 mg/ml) of fifteen MS patients varied in different ranges
Summary
Multiple sclerosis (MS) is a chronic demyelinating pathology of the central nervous system presenting a serious medical and social problem. The T-cell immune system plays a leading role in MS pathogenesis, normal functioning of the B-cell system is important for the disease development. New keys for understanding MS pathogenesis have appeared after cloning IgG repertoire directly from active plaques and periplaque regions in MS brains and from B-cells recovered from the cerebrospinal fluid of a patient with MS with a subacute disease [2]. DNA-specific monoclonal Abs derived from two MS individuals as well as a DNA-specific Ab derived from a systemic lupus erythematosus (SLE) patient bound efficiently to the surface of neuronal cells and oligodendrocytes. For these Abs, cell-surface recognition was DNA-dependent. The findings indicate that antiDNA Abs may promote important neuropathologic mechanisms in chronic inflammatory disorders, such as MS and SLE [2]
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