Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis.

Abstract:

:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of unknown cause that afflicts the central nervous system. MS is typified by a highly clonally restricted antigen-driven antibody response that is confined largely to the central nervous system. The major antigenic targets of this response and the role of antibody in disease pathogenesis remain unclear. To help resolve these issues, we cloned the IgG repertoire directly from active plaque and periplaque regions in MS brain and from B cells recovered from the cerebrospinal fluid of a patient with MS with subacute disease. We found that high-affinity anti-DNA antibodies are a major component of the intrathecal IgG response in the patients with MS that we studied. Furthermore, we show DNA-specific monoclonal antibodies rescued from two subjects with MS as well as a DNA-specific antibody rescued from an individual suffering from systemic lupus erythematosus bound efficiently to the surface of neuronal cells and oligodendrocytes. For two of these antibodies, cell-surface recognition was DNA dependent. Our findings indicate that anti-DNA antibodies may promote important neuropathologic mechanisms in chronic inflammatory disorders, such as MS and systemic lupus erythematosus.

authors

Williamson RA,Burgoon MP,Owens GP,Ghausi O,Leclerc E,Firme L,Carlson S,Corboy J,Parren PW,Sanna PP,Gilden DH,Burton DR

doi

10.1073/pnas.031567598

keywords:

subject

Has Abstract

pub_date

2001-02-13 00:00:00

pages

1793-8

issue

4

eissn

0027-8424

issn

1091-6490

pii

031567598

journal_volume

98

pub_type

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