title: Induction of experimental autoimmune neuritis with peripheral myelin protein-22.
abstract: Two myelin proteins, P2 basic protein and P0 glycoprotein, can induce experimental autoimmune neuritis (EAN), a model of human inflammatory neuropathy. We investigated whether peripheral nerve myelin protein-22 (PMP22), the gene for which is duplicated in hereditary motor sensory neuropathy type la, can also induce EAN. PMP22 cDNA produced by the reverse transcriptase-polymerase chain reaction from rat sciatic nerve was expressed in Escherichia coli as a fusion protein with glutathione-S-transferase (GST). Ten Lewis rats were immunized with purified PMP22 fusion protein (50-100 microg) and eight controls with the same amount of GST. Two additional animals were immunized with each of two peptides (250 microg) of the human PMP22 extracellular sequences. Animals were examined daily until 20 days following immunization, when they underwent neurophysiological examination. A serum sample was then taken, prior to perfusion with glutaraldehyde and removal of the sciatic nerves and cauda equina. PMP22-immunized animals developed antibodies to the fusion protein and five out of 10 developed limp tails. No changes were observed in controls immunized with GST or in animals immunized with peptide. The mean compound motor action potentials elicited in the foot muscles by stimulation of the sciatic nerve at the sciatic notch and of the tibial nerve at the ankle were significantly reduced in the PMP22-immunized group (P < 0.05). Spinal roots from the group of animals immunized with PMP22 showed sparse infiltration of mononuclear cells, oedema and demyelination. PMP22 now deserves consideration as an autoantigen in human acute inflammatory demyelinating polyradiculoneuropathy.
authors.affiliation: Department of Neurology, UMDS, Guy's Hospital, London, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Gabriel
authors.forename: R A
authors.initials: RA
authors.lastname: Hughes
authors.forename: S E
authors.initials: SE
authors.lastname: Moore
authors.forename: K J
authors.initials: KJ
authors.lastname: Smith
authors.forename: F S
authors.initials: FS
authors.lastname: Walsh
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000502:physiology; D002420:Cauda Equina / Q000473:pathology; D003711:Demyelinating Diseases / Q000473:pathology; D006801:Humans; D008297:Male; D009185:Myelin Proteins / Q000276:immunology*; D009186:Myelin Sheath / Q000648:ultrastructure; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; C489546:Pmp22 protein, rat