title: The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.
abstract: Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction.
authors.affiliation: Department of Microbiology and Immunology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America; The Harriet and John Wooten Laboratory for Alzheimer's and Neurodegenerative Disease Research, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Curtis
authors.affiliation: Department of Microbiology and Immunology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America; The Harriet and John Wooten Laboratory for Alzheimer's and Neurodegenerative Disease Research, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Najla
authors.initials: N
authors.lastname: Taslim
authors.affiliation: The Department of Physiology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Reece
authors.affiliation: Department of Microbiology and Immunology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America; The University of Chicago, Department of Neurology, Chicago, IL, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Grebenciucova
authors.affiliation: The Department of Physiology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Ray
authors.affiliation: The Department of Comparative Medicine, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Rosenbaum
authors.affiliation: The Department of Physiology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wardle
authors.affiliation: The Department of Physiology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Van Scott
authors.affiliation: Department of Microbiology and Immunology, East Carolina University Brody School of Medicine, Greenville, NC, United States of America; The Harriet and John Wooten Laboratory for Alzheimer's and Neurodegenerative Disease Research, East Carolina University Brody School of Medicine, Greenville, NC, United States of America.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Mannie
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology; D008297:Male; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D007074:Immunoglobulin G; D063308:Myelin-Oligodendrocyte Glycoprotein; D007371:Interferon-gamma