Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 165, Issue 1-2, Pages 104-113Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2005.04.022
Keywords
autoimmunity; autoantibodies; lupus; blood-brain barrier; cerebrospinal fluid; immunoglobulin; albumin; Fluoro Jade B; Western blotting; mass spectrometry; MRL mice
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Funding
- NIAMS NIH HHS [R21 AR049163, 1R21 AR49163-01] Funding Source: Medline
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The systemic autoimmune disease lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric manifestations and brain lesions of unknown etiology. The MRL-lpr mice show behavioral dysfunction concurrent with progression of a lupus-like disease, thus providing a valuable model in understanding the pathogenesis of autoimmunity-induced CNS damage. Profound neurodegeneration in the limbic system of MRL-lpr mice is associated with cytotoxicity of their cerebrospinal fluid (CSF) to mature and immature neurons. We have recently shown that IgG-rich CSF fraction largely accounts for this effect. The present study examines IgG levels in serum and CSF, as well as the permeability of the blood-brain barrier in mice that differ in immune status, age, and brain morphology. In comparison to young MRL-lpr mice and age-matched congenic controls, a significant elevation of IgG and albumin levels were detected in the CSF of aged autoimmune MRL-lpr mice. Two-dimensional gel electrophoresis and MALDI-TOF MS confirmed elevation in IgG heavy and Ig light chain isoforms in the CSF. Increased permeability of the blood-brain barrier correlated with neurodegeneration (as revealed by Fluoro Jade B staining) in periventricular areas. Although the source and specificity of neuropathogenic antibodies remain to be determined, these results support the hypothesis that a breached blood-brain barrier and IgG molecules are involved in the etiology of CNS damage during SLE-like disease. (C) 2005 Elsevier B.V. All rights reserved.
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