RESUMEN
OBJECTIVE: This retrospective study aimed to describe a cohort of 38 pediatric patients with MOGAD and to investigate the clinical differences between patients with CSF-negativity and CSF-positivity for MOG-abs. METHODS: The clinical and laboratory characteristics of pediatric patients with MOGAD were retrospectively studied. Demographics, clinical characteristics, CSF analysis, treatments and prognosis of patients were recorded. All patients' serums and CSF were tested for MOG-IgG by live cell-based assays (CBA). The data were statistically analysed. RESULTS: A total of 38 pediatric MOGAD patients were enrolled in the study, including 22 (57.9 %) females and 16 male (42.1 %) with a mean age of 8.4 ± 4.0 years at disease onset. Twenty-seven (71.7 %) patients were CSF-positive for MOG-abs while 11 (28.9 %) patients were CSF-negative for MOG-abs. The median follow-up was 25.5 months (IQR 5.5-73.25). Seventeen (44.7 %) patients presented a relapsing disease course, and the majority of these patients was CSF positive with a significant difference between the two groups (p = 0.038) in terms of recurrent diseases. CSF-positive patients presented more often an increased white cell count (p = 0.043), and in this cohort clinical phenotypes with spinal involvement were more frequent while encephalitis-like phenotypes were more frequent in the CSF negative cohort (p = 0.019). CONCLUSIONS: CSF-status appears to identify two subgroups in this pediatric MOGAD population; thus, CSF-status requires further studies in pediatric patients with MOGAD.
Asunto(s)
Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Humanos , Masculino , Femenino , Glicoproteína Mielina-Oligodendrócito/inmunología , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Niño , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Estudios Retrospectivos , Preescolar , Adolescente , Estudios de Seguimiento , Relevancia ClínicaRESUMEN
The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.
Asunto(s)
Encefalitis , Inmunoglobulina G , Esclerosis Múltiple , Glicoproteína Mielina-Oligodendrócito , Mielitis , Neuromielitis Óptica , Neuritis Óptica , Humanos , Acuaporina 4 , Autoanticuerpos , Estudios Transversales , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico , Glicoproteína Mielina-Oligodendrócito/sangre , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeoRESUMEN
We report the case of a patient with symptoms of anti-NMDAR encephalitis and anti-MOG associated disease simultaneously, in whom the identification of antibodies guided to a more aggressive treatment strategy, resulting in a good clinical outcome. MRI is an important tool to diagnose this kind of patients. The co-occurrence of both diseases in infrequent, but atypical symptoms should increase our awareness of the possibility of an overlap syndrome.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico por imagen , Autoanticuerpos/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Humanos , MasculinoRESUMEN
OBJECTIVE: To elucidate the differences in the source and in the level of intrathecal synthesis between anti-aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). METHODS: Thirty-eight patients with MOG-IgG-associated disease and 36 with AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) were studied for the antibody titers in the sera and CSF simultaneously collected in the acute attacks. The quotients between CSF and serum levels of albumin, total immunoglobulin G, and each disease-specific antibody were calculated. Intrathecal production level in each disease-specific antibody was evaluated by calculating the antibody index from these quotients. RESULTS: Eleven of the 38 patients with MOG-IgG were positive for the antibody only in the CSF, while no patient with AQP4-IgG showed CSF-restricted AQP4-IgG. Blood-brain barrier compromise as shown by raised albumin quotients was seen in 75.0% of MOG-IgG-positive cases and 43.8% of AQP4-IgG-positive cases. Moreover, MOG-IgG quotients were >10 times higher than AQP4-IgG quotients (effect size r = 0.659, p < 0.0001). Elevated antibody index (>4.0) was confirmed in 12 of 21 with MOG-IgG, whereas it was seen only in 1 of 16 with AQP4-IgG (φ = 0.528, p < 0.0001). The CSF MOG-IgG titers (ρ = 0.519, p = 0.001) and antibody indexes for MOG-IgG (ρ = 0.472, p = 0.036) correlated with the CSF cell counts but not with clinical disability. CONCLUSIONS: Intrathecal production of MOG-IgG may occur more frequently than that of AQP4-IgG. This finding implies the different properties of B-cell trafficking and antibody production between MOG-IgG-associated disease and AQP4-IgG-positive NMOSD.
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Anticuerpos Bloqueadores/líquido cefalorraquídeo , Acuaporina 4/inmunología , Inmunoglobulina G/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/inmunología , Adolescente , Adulto , Albúminas/análisis , Algoritmos , Anticuerpos Antiidiotipos , Especificidad de Anticuerpos , Acuaporina 4/líquido cefalorraquídeo , Barrera Hematoencefálica/patología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Médula Espinal/inmunología , Médula Espinal/metabolismo , Adulto JovenRESUMEN
Neurocysticercosis (NC) presents two broad clinical entities: extraparenchymal (EP-NC) and parenchymal (P-NC). Using ELISA methodology, we demonstrate autoantibodies to tubulin and the Major oligodendrocyte glycoprotein (MOG) in the CSF of most, but not all, EP-NC samples. Levels of these autoantibodies were considerably reduced or absent in the P-NC samples. There was a striking correlation between levels of anti-tubulin and anti-MOG, and the significant correlation between the levels of autoantibodies and cellularity in the CSF, suggests that stimulation of the autoantibody response may be a function of cerebral inflammation. A hypothetical model to describe the pathogenesis of EP-NC is presented.
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Autoanticuerpos/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Neurocisticercosis/líquido cefalorraquídeo , Neurocisticercosis/diagnóstico por imagen , Tubulina (Proteína)/líquido cefalorraquídeo , Animales , Biomarcadores/líquido cefalorraquídeo , Ecuador/epidemiología , Humanos , México/epidemiología , Neurocisticercosis/epidemiología , Tejido Parenquimatoso/metabolismo , Fragmentos de Péptidos/líquido cefalorraquídeo , PorcinosAsunto(s)
Autoanticuerpos/líquido cefalorraquídeo , Betacoronavirus , Infecciones por Coronavirus/líquido cefalorraquídeo , Infecciones por Coronavirus/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Neumonía Viral/líquido cefalorraquídeo , Neumonía Viral/diagnóstico por imagen , Adulto , Biomarcadores/líquido cefalorraquídeo , COVID-19 , Femenino , Humanos , Pandemias , SARS-CoV-2RESUMEN
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorders are increasingly recognized as a distinct disease entity. However, diagnostic sensitivity and specificity of serum MOG-IgG as well as recommendations for testing are still debated. MATERIALS AND METHODS: Between October 2015 and July 2017 we tested serum MOG-IgG in 91 adult patients (49 females) with a demyelinating event (DE) not fulfilling 2010 McDonald criteria for MS at sampling, negative for neuromyelitis optica (NMO)-IgG and followed-up for at least 12 months. We assessed the sensitivity and specificity of a live-cell MOG-IgG assay for each final diagnosis at last follow-up, for the 2018 international recommendations for MOG-IgG testing, and for other combinations of clinical and laboratory characteristics. RESULTS: Clinical presentations included acute myelitis (n = 48), optic neuritis (n = 36), multifocal encephalomyelitis (n = 4), and brainstem syndrome (n = 3). Twenty-four patients were MOG-IgG positive. Sensitivity and specificity of MOG-IgG test applied to the 2018 international recommendations were 28.4% and 86.7%, while they were 42.1% and 88.6% when applied to DE of unclear aetiology as defined above with two or more among: 1_no periventricular and juxtacortical MS-like lesions on brain MRI; 2_longitudinally extensive MRI optic nerve lesion; 3_no CSF-restricted oligoclonal bands; 4_CSF protein > 50 mg/dl. CONCLUSIONS: Simplified requirements compared to those currently proposed for MOG-IgG testing could facilitate the applicability of the assay in the diagnosis of adults with DEs of unclear aetiology.
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/diagnóstico por imagen , Inmunoglobulina G/sangre , Glicoproteína Mielina-Oligodendrócito/sangre , Adulto , Anciano , Autoanticuerpos/líquido cefalorraquídeo , Estudios de Cohortes , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Femenino , Estudios de Seguimiento , Células HEK293 , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Adulto JovenRESUMEN
BACKGROUND: Autoantibodies against myelin oligodendrocyte glycoprotein (anti-MOG-Abs) occur in a majority of children with acquired demyelinating syndromes (ADS) and physiopathology is still under investigation. As cynomolgus macaques immunized with rhMOG, all develop an experimental autoimmune encephalomyelitis (EAE), we assessed relatedness between anti-MOG-Abs associated diseases in both species. METHODS: The study includes 27 children followed for ADS and nine macaques with rhMOG-induced EAE. MRI lesions, cytokines in blood, and CSF at onset of ADS or EAE, as well as histopathological features of brain lesions were compared. RESULTS: Twelve children with anti-MOG-Abs ADS (ADS MOG+) and nine macaques with EAE, presented increased IL-6 and G-CSF in the CSF, whereas no such signature was found in 15 ADS MOG-. Furthermore, IgG and C1q were associated to myelin and phagocytic cells in brains with EAE (n = 8) and in biopsies of ADS MOG+ (n = 2) but not ADS MOG- children (n = 1). Macaque brains also revealed prephagocytic lesions with IgG and C1q depositions but no leukocyte infiltration. CONCLUSIONS: Children with ADS MOG+ and macaques with EAE induced with rhMOG, present a similar cytokine signature in the CSF and a comparable aspect of brain lesions indicating analogous pathophysiological processes. In EAE, prephagocytic lesions points at IgG as an initial effector of myelin attack. These results support the pertinence of modeling ADS MOG+ in non-human primates to apprehend the natural development of anti-MOG-associated disease, find markers of evolution, and above all explore the efficacy of targeted therapies to test primate-restricted molecules.
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Autoanticuerpos/sangre , Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/diagnóstico por imagen , Encefalomielitis Autoinmune Experimental/sangre , Encefalomielitis Autoinmune Experimental/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/sangre , Adolescente , Animales , Autoanticuerpos/líquido cefalorraquídeo , Niño , Preescolar , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Encefalomielitis Autoinmune Experimental/líquido cefalorraquídeo , Femenino , Humanos , Macaca , Masculino , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeoRESUMEN
Recently, we documented two Japanese cases of myelin-oligodendrocyte glycoprotein (MOG) antibody-associated relapsing encephalitis among patients who had been diagnosed with probable neuro-Behçet's disease (NBD). They presented partial systemic BD symptoms, brainstem lesions, and the human leukocyte antigen (HLA) B51 allele and responded well to steroid therapy. Our cases suggest that we need to differentiate anti-MOG antibody-associated encephalitis from probable NBD because both disorders can present with brainstem or cerebral lesions, CSF pleocytosis, and elevated levels of CSF IL-6 and respond to steroid treatment. Furthermore, oral ulceration, skin lesions, and HLA-B51 might be observed nonspecifically in patients with anti-MOG antibody-associated encephalitis.
Asunto(s)
Síndrome de Behçet/líquido cefalorraquídeo , Síndrome de Behçet/diagnóstico por imagen , Encefalitis/líquido cefalorraquídeo , Encefalitis/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Adulto , Femenino , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE OF REVIEW: This article provides an up-to-date summary of the categories, diagnosis, and management of pediatric demyelinating disorders. RECENT FINDINGS: Understanding of the diverse spectrum of pediatric demyelinating disorders, including monophasic and multiphasic forms, has improved. Pediatric multiple sclerosis (MS) is the most common demyelinating disorder in children, and recent genetic and environmental risk research has clarified that pediatric MS is on the same continuum of disease as adult MS. Recent advances in the treatment of pediatric MS include clinical trials leading to regulatory agency-approved treatments. The identification of myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies in children has been a major advance, allowing for appropriate treatment and management of these syndromes. SUMMARY: Antibody testing is now helping to define subtypes of pediatric demyelinating disorders, including myelin oligodendrocyte glycoprotein-seropositive and aquaporin-4-seropositive cases that are distinct from pediatric MS. Treatments for pediatric MS are being evaluated in clinical trials.
Asunto(s)
Acuaporina 4/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/diagnóstico por imagen , Adolescente , Niño , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/tratamiento farmacológico , Encefalomielitis/líquido cefalorraquídeo , Encefalomielitis/diagnóstico por imagen , Encefalomielitis/tratamiento farmacológico , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Ácido Micofenólico/administración & dosificación , Neuromielitis Óptica/tratamiento farmacológicoRESUMEN
OBJECTIVE: Determination of glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and myelin oligodendrocyte glycoprotein (MOG) levels in cerebrospinal fluid (CSF), and astrocytic damage analysis in patients with GFAP astrocytopathy (GFAP-A) and other conditions. METHODS: GFAP, AQP4, and MOG levels in CSF were detected via enzyme-linked immunosorbent assays. Anti-GFAP, anti-AQP4, and anti-MOG IgGs were detected via indirect immunofluorescence assays. RESULTS: In 32 GFAP-Astrocytopathy patients, CSF GFAP was significantly higher during acute exacerbation than it was in patients with MOG encephalomyelitis, multiple sclerosis, autoimmune encephalitis, and an "other inflammatory neurological disorders" group (all p < 0.0001). CSF GFAP levels were slightly higher in the GFAP-A group than in an anti-AQP4 IgG-positive neuromyelitis optica spectrum disorder group (pâ¯=â¯0.012). There were no significant differences between the CSF MOG and AQP4 levels in the GFAP-A group and those of other groups. CSF GFAP levels were significantly reduced after steroid treatment (pâ¯=â¯0.011). CSF GFAP levels differed significantly in GFAP-Astrocytopathy patients with and without encephalitis (pâ¯=â¯0.016). In GFAP-Astrocytopathy patients, CSF GFAP was correlated with Expanded Disability Status Scale (EDSS) score during attack (râ¯=â¯0.545, pâ¯=â¯0.001). In follow-up examinations however, in GFAP-Astrocytopathy patients CSF GFAP level was not correlated with EDSS score 6 months later. CONCLUSIONS: CSF GFAP level and pathological examination of GFAP-Astrocytopathy patients revealed astrocyte damage. CSF GFAP level was associated with steroid treatment at the acute stage, therefore CSF GFAP may be a sensitive biomarker with respect to the effects of therapy during the acute stage.
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Acuaporina 4/líquido cefalorraquídeo , Astrocitos/patología , Enfermedades Autoinmunes Desmielinizantes SNC/líquido cefalorraquídeo , Enfermedades Autoinmunes Desmielinizantes SNC/patología , Encefalitis/líquido cefalorraquídeo , Encefalitis/patología , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Acuaporina 4/inmunología , Biomarcadores/líquido cefalorraquídeo , Enfermedades Autoinmunes Desmielinizantes SNC/fisiopatología , Encefalitis/fisiopatología , Femenino , Proteína Ácida Fibrilar de la Glía/inmunología , Humanos , Masculino , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients. METHODS: In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14). RESULTS: In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases. CONCLUSIONS: The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets.
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Acuaporina 4/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Inmunoglobulina G/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Neuromielitis Óptica/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/terapia , Adulto JovenRESUMEN
In the current study, we conducted a quantitative in-depth proteome and deglycoproteome analysis of cerebrospinal fluid (CSF) from relapsing-remitting multiple sclerosis (RRMS) and neurological controls using mass spectrometry and pathway analysis. More than 2000 proteins and 1700 deglycopeptides were quantified, with 484 proteins and 180 deglycopeptides significantly changed between pools of RRMS and pools of controls. Approximately 300 of the significantly changed proteins were assigned to various biological processes including inflammation, extracellular matrix organization, cell adhesion, immune response, and neuron development. Ninety-six significantly changed deglycopeptides mapped to proteins that were not found changed in the global protein study. In addition, four mapped to the proteins oligo-myelin glycoprotein and noelin, which were found oppositely changed in the global study. Both are ligands to the nogo receptor, and the glycosylation of these proteins appears to be affected by RRMS. Our study gives the most extensive overview of the RRMS affected processes observed from the CSF proteome to date, and the list of differential proteins will have great value for selection of biomarker candidates for further verification.
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Proteínas del Líquido Cefalorraquídeo/genética , Matriz Extracelular/genética , Esclerosis Múltiple Recurrente-Remitente/genética , Glicoproteína Mielina-Oligodendrócito/genética , Proteoma/genética , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Adhesión Celular , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Proteínas del Líquido Cefalorraquídeo/inmunología , Matriz Extracelular/inmunología , Proteínas de la Matriz Extracelular/líquido cefalorraquídeo , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/inmunología , Expresión Génica , Glicoproteínas/líquido cefalorraquídeo , Glicoproteínas/genética , Glicoproteínas/inmunología , Humanos , Inmunidad Innata , Inflamación , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/patología , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/inmunología , Neurogénesis/genética , Neurogénesis/inmunología , Receptor Nogo 1/genética , Receptor Nogo 1/inmunología , Receptor Nogo 1/metabolismo , Mapeo de Interacción de Proteínas , Proteoma/inmunología , Proteoma/metabolismoRESUMEN
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. METHODS: Data including the patients' serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables. RESULTS: Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (Δ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = -3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; Δ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; Δ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups. CONCLUSION: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.
Asunto(s)
Esclerosis Múltiple/patología , Neuromielitis Óptica/patología , Adolescente , Adulto , Acuaporina 4/sangre , Acuaporina 4/líquido cefalorraquídeo , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Enfermedades Desmielinizantes/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/sangre , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Neuromielitis Óptica/sangre , Neuromielitis Óptica/líquido cefalorraquídeo , Estudios Retrospectivos , Adulto JovenRESUMEN
Acquired demyelinating syndromes (ADS) in children evolve either as a monophasic disease diagnosed as acute demyelinating encephalomyelitis (ADEM), transverse myelitis (TM) or optic neuritis (ON), or a multiphasic one with several relapses most often leading to the diagnosis of multiple sclerosis (MS) or neuromyelitis optica (NMO). These neuroinflammatory disorders are increasingly associated with autoantibodies against proteins such as aquaporin-4 in rare instances, and more frequently against myelin oligodendrocyte glycoprotein (MOG). Recently, in adult NMO patients, C5a levels were shown to be elevated in cerebrospinal fluid (CSF) during acute exacerbation. We investigated the CSF levels of anaphylatoxins and pro-inflammatory cytokines, and plasma MOG antibodies in onset samples from children with ADS. Thirty four children presenting with a first episode of ADS, 17 with monophasic ADS (9 with ADEM, 4 with TM and 4 with ON) and 17 with MS, who had paired blood and CSF samples at onset were included and compared to 12 patients with other non-inflammatory neurological disorders (OND). Cytokines and anaphylatoxins in CSF were measured by Cytometric Bead Array immunoassay. MOG antibody titers in plasma were tested by flow cytometry using a stable cell line expressing full-length human MOG. We found a significant increase in C5a levels in the CSF of patients with monophasic ADS (n=17) compared to OND (n=12, p=0.0036) and to MS (n=17, p=0.0371). The C5a levels in MS were higher than in OND without reaching significance (p=0.2). CSF IL-6 levels were significantly increased in monophasic ADS compared to OND (p=0.0027) and to MS (p=0.0046). MOG antibody plasma levels were significantly higher in monophasic ADS (p<0.0001) and, to a lesser extent, in MS compared to OND (p=0.0023). Plasma MOG antibodies and CSF IL-6 levels were significantly correlated (r=0.51, p=0.018). CSF C5a and IL-6 levels are increased in monophasic ADS but not in MS when compared to OND, suggesting that these markers may help to predict monophasic or relapsing fate of ADS at onset. MOG antibody titers, which were higher in monophasic ADS than in MS, correlated with IL-6 levels, but not with C5a, suggesting an association between MOG antibodies and neuroinflammation in pediatric ADS.
Asunto(s)
Enfermedades Desmielinizantes , Inmunoglobulina G/sangre , Interleucina-6/inmunología , Esclerosis Múltiple , Glicoproteína Mielina-Oligodendrócito/inmunología , Adolescente , Anafilatoxinas/líquido cefalorraquídeo , Anafilatoxinas/inmunología , Anafilatoxinas/metabolismo , Niño , Citocinas/metabolismo , Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Enfermedades Desmielinizantes/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Estudios Longitudinales , Masculino , Esclerosis Múltiple/sangre , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Glicoproteína Mielina-Oligodendrócito/sangre , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Estudios RetrospectivosRESUMEN
BACKGROUND: The complex pathogenesis of multiple sclerosis, combined with an unpredictable prognosis, requires identification of disease-specific diagnostic and prognostic biomarkers. OBJECTIVE: To determine whether inflammatory proteins, such as neurofilament light chain, myelin oligodendrocyte glycoprotein and myelin basic protein, and neurodegenerative proteins, such as tau and glial fibrillary acidic protein, can serve as biomarkers for predicting the clinical subtype and prognosis of MS. METHODS: Cerebrospinal fluid and serum samples were collected from patients with a diagnosis of clinically isolated syndrome (n = 46), relapsing-remitting MS (n = 67) or primary-progressive MS (n = 22) along with controls having other non-inflammatory neurological disease (n = 22). Western blot analyses were performed for the listed proteins. Protein levels were compared among different clinical subtypes using one-way analysis of variance analysis. The k-nearest neighbour algorithm was further used to assess the predictive use of these proteins for clinical subtype classification. RESULTS: The results showed that each of tau, GFAP, MOG and NFL protein concentrations differed significantly (p < 0.001) in multiple sclerosis clinical subtypes compared with the controls. Levels of the proteins also differed between the multiple sclerosis clinical subtypes, which may be associated with the underlying disease process. Classification studies revealed that these proteins might be useful for identifying multiple sclerosis clinical subtypes. CONCLUSIONS: We showed that select biomarkers may have potential in identifying multiple sclerosis clinical subtypes. We also showed that the predictive value of the prognosis increased when using a combination of the proteins versus using them individually.