Glycosphingolipid antibodies and blood-nerve barrier in autoimmune demyelinative neuropathy.
OBJECTIVE
To evaluate morphologic changes in small endoneurial vessels in patients with autoimmune demyelinative neuropathy and antiglycosphyngolipid antibodies.


BACKGROUND
Although a humoral immune cause has been postulated for various demyelinating neuropathies, the mechanism by which large molecules like immunoglobulins can traverse the blood-nerve barrier (BNB) to enter the endoneurium is not understood.


METHODS
We examined histologic and ultrastructural changes in small endoneurial vessels in sural nerve biopsy specimens from autoimmune demyelinative neuropathy patients, with or without anti-glycosphingolipid (GSL) antibodies. Density of small endoneurial vessels, mean endothelial area, mean luminal area, and the percentage of endothelial cell junctions (that make up the BNB) that showed evidence of disruption were evaluated.


RESULTS
Only junctional disruption showed a significant difference: autoimmune demyelinative neuropathy patients with anti-GSL antibodies showed more BNB disruption than autoimmune demyelinative neuropathy patients without antibodies or control patients with nonautoimmune neuropathies. The most commonly observed endoneurial change in antibody-positive autoimmune demyelinative neuropathy patients was the finding of continuous, patent spaces lacking tight junctions between endothelial cells.


CONCLUSIONS
Brain endothelial cells and endoneurial endothelial cells share various GSL antigens, including GM1 and GD1b gangliosides, with peripheral nerve tissues. Circulating anti-GSL antibodies could damage cell-to-cell attachments in endoneurial endothelium. This barrier disruption may permit the large molecules like immunoglobulins to enter the endoneurial space, contributing to development of autoimmune demyelinative neuropathy.
Kanda
T
T
Department of Neurology, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan. t-kanda.nuro@med.tmd.ac.jp
Yamawaki
M
M
Iwasaki
T
T
Mizusawa
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000032:analysis*; D002199:Capillary Permeability / Q000276:immunology*; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D006028:Glycosphingolipids / Q000276:immunology*; D006801:Humans; D007365:Intercellular Junctions / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure; D011129:Polyradiculoneuropathy / Q000276:immunology* / Q000473:pathology; D013497:Sural Nerve / Q000098:blood supply / Q000473:pathology / Q000648:ultrastructure
D001323:Autoantibodies; D006028:Glycosphingolipids; D005677:G(M1) Ganglioside