title: Antibody association with a novel model for primary progressive multiple sclerosis: induction of relapsing-remitting and progressive forms of EAE in H2s mouse strains.
abstract: Multiple sclerosis (MS) can be divided into 4 clinical forms: relapsing-remitting (RR), primary progressive (PP), secondary progressive (SP), and progressive relapsing (PR). Since PP-MS is notably different from the other forms of MS, both clinically and pathologically, the question arises whether PP-MS is immunologically similar to the other forms. The pathogenesis of the PP-MS remains unclear, partly due to a lack of highly relevant animal models. Using an encephalitogenic peptide from myelin oligodendrocyte glycoprotein (MOG)92-106, we have established animal models that mimic different forms of MS in 2 strains of H-2s mice, SJL/J and A.SW. We induced experimental allergic encephalomyelitis (EAE) using MOG92-106 in the presence or absence of supplemental Bordetella pertussis (BP). Although, SJL/J mice developed RR-EAE whether BP was given or not, A.SW mice developed PP-EAE without BP and SP-EAE with BP. Histologically, SJL/J mice developed mild demyelinating disease with T cell infiltration, while A.SW mice developed large areas of plaque-like demyelination with immunoglobulin deposition and neutrophil infiltration, but with minimal T cell infiltration. In A.SW mice without BP, high titer serum anti-MOG antibody was detected and the anti-MOG IgG2a/IgG1 ratio correlated with survival times of mice. We hypothesized that, in A.SW mice, a Th2 response favors production of myelinotoxic antibodies, leading to progressive forms with early death. Our new models indicate that a single encephalitogen could induce either RR-, PP-, or SP- forms of demyelinating disease in hosts with immunologically different humoral immune responses.
authors.affiliation: Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132, USA.
authors.forename: I
authors.initials: I
authors.lastname: Tsunoda
authors.forename: L Q
authors.initials: LQ
authors.lastname: Kuang
authors.forename: D J
authors.initials: DJ
authors.lastname: Theil
authors.forename: R S
authors.initials: RS
authors.lastname: Fujinami
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis*; D002490:Central Nervous System / Q000473:pathology; D004269:DNA, Bacterial / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007136:Immunoglobulins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009420:Nervous System / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D010957:Plasmids / Q000235:genetics
chemical_list: D000906:Antibodies; D004269:DNA, Bacterial; D007136:Immunoglobulins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments