Autoimmunoreactivity to Schwann cells in patients with inflammatory neuropathies.
Inflammatory demyelinating neuropathies are characterized by a loss of peripheral nerve myelin. Myelin breakdown is thought to result from an autoimmune reaction towards nerve components. Schwann cells play a crucial role in the synthesis and maintenance of peripheral nerve myelin. An immune attack targeting Schwann cells could therefore affect myelin integrity, leading to disease. We studied the reactivity of sera from patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) towards Schwann cells using immunofluorescence microscopy. We found 24% of the GBS (56 out of 233) and 26% of the CIDP (12 out of 46) patients to have circulating immunoglobulin G autoantibodies against proliferating, non-myelinating human Schwann cells. In contrast, healthy donors showed positive staining in only two out of 34 sera. No reaction was found with sera from patients with non-inflammatory neurological disorders. Immunofluorescence was localized at the distal tips (leading lamella) of the Schwann cell processes. Distal tips of neurites (nerve-growth-cones) of in vitro differentiated non-myelinated hNT2 neurons also stained strongly. GBS and CIDP serum immunoreactivity was also observed in teased nerve fibre preparations. These data suggest that, at least part of the immunoreactivity is not directed against myelin, but towards non-myelin proteins and epitopes possibly involved in Schwann cell-axon interaction.
Kwa
Marcel S G
MS
Department of Neurology, Academic Medical Centre, University of Amsterdam, The Netherlands. m.s.kwa@amc.uva.nl
van Schaik
Ivo N
IN
De Jonge
Rosalein R
RR
Brand
Anneke
A
Kalaydjieva
Luba
L
van Belzen
Nico
N
Vermeulen
Marinus
M
Baas
Frank
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D018929:Cell Culture Techniques / Q000379:methods; D002648:Child; D000939:Epitopes / Q000276:immunology; D005260:Female; D020275:Guillain-Barre Syndrome / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009186:Myelin Sheath / Q000276:immunology; D009412:Nerve Fibers / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000276:immunology*; D012583:Schwann Cells / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D007106:Immune Sera; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins