RESUMO
OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-seropositive pediatric demyelinating syndromes. METHODS: Serum samples collected from 74 children with suspected demyelinating disorders whom were being followed at Massachusetts General Hospital were incubated with control green fluorescent protein (GFP)- and MOG-GFP-transfected Jurkat cell clones. The binding ratios were calculated using flow cytometry. Using statistical analyses, we compared the demographic, clinical and radiological features in our seropositive and seronegative patients. RESULTS: We found that 13 out of 74 (17.5%) patients were seropositive for MOG. The MOG-seropositive patients were younger than the seronegative patients (p = 0.049). No single disease category predominated among the seropositive patients, nor was one group more likely to have a polyphasic course. There were two out of four neuromyelitis optica (NMO) patients who had MOG antibodies; both were seronegative for aquaporin -4 (AQP4) antibodies. One had monophasic disease and the other had frequent relapses. There was a bimodal distribution of the MOG-seropositive patients by age at onset, with a distinct younger group (4-8 years) having a high prevalence of encephalopathy and an older group (13-18 years), whom presented almost exclusively with optic neuritis. MRI analysis demonstrated the absence of corpus callosum lesions in the seropositive patients (p = 0.012). The annualized relapse rate (ARR) and the Expanded Disability Status Scale (EDSS) results at 2 years did not differ between the seropositive and seronegative patients. CONCLUSION: MOG antibodies are found across a variety of pediatric demyelinating syndromes having some distinct clinical and MRI features.
Assuntos
Autoanticorpos/imunologia , Encéfalo/patologia , Encefalomielite Aguda Disseminada/imunologia , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/imunologia , Neurite Óptica/imunologia , Medula Espinal/patologia , Adolescente , Aquaporina 4/imunologia , Criança , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/patologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/fisiopatologia , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Feminino , Citometria de Fluxo , Humanos , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Neuromielite Óptica/patologia , Neuromielite Óptica/fisiopatologia , Neurite Óptica/patologia , Neurite Óptica/fisiopatologia , FenótipoRESUMO
Studies of the underlying immune mechanisms of multiple sclerosis (MS) in children may shed light on the initial events of MS pathogenesis. We studied T cell responses to myelin peptides in 10 pediatric MS patients (PMS), 10 pediatric healthy controls (PHC), 10 adult MS patients (AMS) and 10 adult healthy controls (AHC). A significantly higher proportion of divided CD4+ T cell responses in response to myelin peptides by the CFSE assay in PMS compared to PHC at both concentrations of myelin peptide tested (t test, 95% CI, p=0.0067 for MP1; p=0.0086 for MP10), and between PMS and AMS (p=0.0012 at 1 µg/mL of myelin peptides, p<0.0001 at 10 µg/mL) was found. In addition, T cells with a central memory phenotype producing IL-17 were increased in PMS compared to PHC (p<0.05). IL-7 levels in culture supernatants were elevated in PMS compared to PHC and AMS (t test<0.01).
Assuntos
Linfócitos T CD4-Positivos/imunologia , Citocinas/imunologia , Esclerose Múltipla/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas da Mielina/imunologia , Peptídeos/imunologia , Adulto JovemRESUMO
To assess the effects and mechanisms of a CD200R1 agonist administered during the progressive stage of a multiple sclerosis model, we administered CD200R1 agonist (CD200Fc) or control IgG2a during the chronic phase of disease (days 10-30) in mice with experimental autoimmune encephalomyelitis (EAE), induced using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) peptide. We found that administration of CD200Fc during the chronic stages of EAE reduced disease severity, demyelination, and axonal damage, through the modulation of several key disease mechanisms. CD200Fc treatment suppressed macrophage and microglial accumulation within the CNS, in part through downregulation of adhesion molecules VLA-4 and LFA-1, which are necessary for macrophage migration. Additionally, expression of activation markers MHC-II and CD80 and production of proinflammatory cytokines IL-6, tumor necrosis factor-alpha, and nitric oxide by CD11b(+) cells were decreased in both the spleen and CNS in CD200Fc-treated animals. Antigen-presenting cell function in the spleen and CNS was suppressed in CD200Fc-treated mice, but there were no significant alterations on T cell activation or phenotype. CD200Fc increased apoptosis of CD11b(+) cells but not astrocytes. In contrast, addition of CD200Fc treatment protected oligodendrocytes from apoptosis in vitro and in vivo. Our results demonstrate that CD200R1 agonists modulate both myeloid- and non-myeloid-related mechanisms of chronic disease in the EAE model and may be effective in the treatment of progressive multiple sclerosis and other neurodegenerative diseases.