Elevated immunoglobulin levels in the cerebrospinal fluid from lupus-prone mice.
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.
Sidor
Michelle M
MM
McMaster University, Department of Psychiatry and Behavioural Neurosciences, 1200 Main Street West, Hamilton, Canada L8N 3Z5.
Sakic
Boris
B
Malinowski
Paul M
PM
Ballok
David A
DA
Oleschuk
Curtis J
CJ
Macri
Joseph
J
D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid; D015180:Electrophoresis, Gel, Two-Dimensional; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D007143:Immunoglobulin Heavy Chains / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000032:analysis; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000134:cerebrospinal fluid*; D008180:Lupus Erythematosus, Systemic / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D002556:Cerebrospinal Fluid Proteins; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins