RESUMO
Echovirus 11 (E11) is a neurotropic virus that occasionally causes fatal neurological diseases in infected children. However, the molecular mechanism underlying the disease and pathological spectrum of E11 infection remains unclear. Therefore, we modelled E11 infection in 2-day-old type I interferon receptor knockout (IFNAR-/-) mice, which are susceptible to enteroviruses, with E11, and identified symptoms consistent with the clinical signs observed in human cases. All organs of infected suckling mice were found to show viral replication and pathological changes; the muscle tissue showed the highest viral replication, whereas the brain and muscle tissues showed the most obvious pathological changes. Brain tissues showed oedema and a large number of dead nerve cells; RNA-Seq analysis of the brain and hindlimb muscle tissues revealed differentially expressed genes to be abundantly enriched in immune response-related pathways, with changes in the Guanylate-binding protein (GBP) and MHC class genes, causing aseptic meningitis-related symptoms. Furthermore, human glioma U251 cell was identified as sensitive target cells for E11 infection. Overall, these results provide new insights into the pathogenesis and progress of aseptic meningitis caused by E11.
Assuntos
Encéfalo/patologia , Encéfalo/virologia , Infecções por Echovirus/patologia , Infecções por Echovirus/virologia , Enterovirus Humano B/fisiologia , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Infecções por Echovirus/genética , Humanos , Meningite Asséptica/genética , Meningite Asséptica/patologia , Meningite Asséptica/virologia , Camundongos , Camundongos Knockout , Músculo Esquelético/patologia , Músculo Esquelético/virologia , RNA-Seq , Receptor de Interferon alfa e beta/genética , Transcriptoma , Carga Viral , Replicação ViralRESUMO
Vogt-Koyanagi-Harada (VKH) syndrome is a rare condition implicating systemic immune reaction against melanocytes. The pathophysiology is unclear. A genetic predisposition has been suggested as HLA-DR4/DRB1*04 is more common among VKH patients. Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2. To date, no case of anti PD-1 -induced VKH syndrome has been described. We report here the case of a HLA-DR4/DRB1*04 patient successfully treated with anti PD-1 for advanced melanoma who developed a systemic immune reaction against melanocytes for whom we discuss a VKH-like syndrome diagnosis in a potentially genetically predisposed patient.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Meningite Asséptica/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Uveíte/diagnóstico , Síndrome Uveomeningoencefálica/diagnóstico , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Predisposição Genética para Doença , Antígeno HLA-DR4/genética , Cadeias HLA-DRB1/genética , Humanos , Imunoterapia/efeitos adversos , Metástase Linfática , Masculino , Melanócitos/imunologia , Melanoma/secundário , Meningite Asséptica/etiologia , Meningite Asséptica/genética , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Neoplasias Cutâneas/secundário , Uveíte/etiologia , Uveíte/genética , Síndrome Uveomeningoencefálica/etiologia , Síndrome Uveomeningoencefálica/genéticaAssuntos
Febre/genética , Meningite Asséptica/genética , Mutação , Mielite/genética , Neutrófilos/imunologia , Pirina/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença Crônica , Análise Mutacional de DNA , Feminino , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/imunologia , Predisposição Genética para Doença , Hereditariedade , Humanos , Imunossupressores/uso terapêutico , Masculino , Meningite Asséptica/diagnóstico , Meningite Asséptica/tratamento farmacológico , Meningite Asséptica/imunologia , Pessoa de Meia-Idade , Mielite/diagnóstico , Mielite/tratamento farmacológico , Mielite/imunologia , Neutrófilos/efeitos dos fármacos , Linhagem , Fenótipo , Recidiva , Indução de Remissão , Resultado do TratamentoRESUMO
Fabry disease can cause various neurological manifestations. We describe the case of a Japanese woman with Fabry disease who presented with ischemic stroke, aseptic meningitis, and psychiatric symptoms. The patient had a mutation in intron 4 of her α-galactosidase A gene, which was not detected in her family. This case suggests that Fabry disease should be considered in young patients who exhibit central nervous system symptoms such as ischemic stroke, even if there is no family history of the condition. The episodes of aseptic meningitis and stroke experienced by our patient suggest that persistent inflammation might be the mechanism underlying Fabry disease.
Assuntos
Isquemia Encefálica/genética , Doença de Fabry/genética , Febre/genética , Cefaleia/genética , Meningite Asséptica/genética , Acidente Vascular Cerebral/genética , Adulto , Isquemia Encefálica/complicações , Depressão/genética , Doença de Fabry/complicações , Feminino , Febre/etiologia , Cefaleia/etiologia , Humanos , Meningite Asséptica/etiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Among Coxsackie B viruses, Coxsckievirus B5 is one of the most predominant serotypes in human, it is frequently associated with cases of neurological diseases, epidemics of meningitis and is a common cause of cardiomyopathy and diabetes. In the present study 27 isolates of Coxsackievirus B5 from North Africa, obtained from cerebrospinal fluid and stool samples of healthy individuals, patients with acute flaccid paralysis or aseptic meningitis were investigated by partial sequencing in the 5' half of the VP1 region and compared to the up-to-date published Coxsackievirus B5 sequences in the same genomic region. Four distinct genomic groups and ten different clusters were individualized. Most of the isolates from Algeria and Tunisia belonged to two clusters. For both, the sequences from North Africa clustered mainly with sequences from European countries, the majority isolated recently during the 2000s. The analysis of the alignment of amino-acids sequences in the VP1 gene revealed four major substitutions in strains from different clusters, we also noticed changes in the BC-loop region; this region is associated with viral antigenicity. This study permit to better identify circulating Coxsackievirus B5 strains throughout the world and their genetic relationship. The protein analysis showed changes that could imply some antigenic significance. J. Med. Virol. 83:1247-1254, 2011. © 2011 Wiley-Liss, Inc.
Assuntos
Proteínas do Capsídeo/genética , Infecções por Coxsackievirus/virologia , Enterovirus Humano B/classificação , Enterovirus Humano B/genética , Meningite Asséptica/virologia , Paraplegia/virologia , Proteínas Virais/genética , África do Norte , Sequência de Aminoácidos , Proteínas do Capsídeo/isolamento & purificação , Linhagem Celular Tumoral , Infecções por Coxsackievirus/líquido cefalorraquidiano , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/genética , Enterovirus Humano B/isolamento & purificação , Enterovirus Humano B/patogenicidade , Epidemias , Europa (Continente) , Genótipo , Humanos , Meningite Asséptica/líquido cefalorraquidiano , Meningite Asséptica/epidemiologia , Meningite Asséptica/genética , Dados de Sequência Molecular , Tipagem Molecular , Paraplegia/líquido cefalorraquidiano , Paraplegia/epidemiologia , Paraplegia/genética , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Virais/isolamento & purificaçãoRESUMO
Canine Steroid-Responsive Meningitis-Arteritis (SRMA) is a suitable animal model for studies on the development of neutrophilic pleocytosis in aseptic meningitis. Samples of dogs in the acute phase of SRMA (n=16) were examined for gene expression of matrix metalloproteinases (MMP)-2 and -9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2. Results were compared to those of dogs under glucocorticosteroid treatment for SRMA (n=16) and dogs with other inflammatory and neoplastic diseases of the central nervous system (CNS) (n=19). Samples included mononuclear (PBMCs) and polymorphonuclear cells (PBPMNs) of peripheral blood and cerebrospinal fluid white blood cells (CSF WBCs). In the acute phase of SRMA CSF WBCs showed mRNA expression for MMP-2 and -9 and TIMP-1 and -2, highlighting a contribution of these cells to the overall content of MMPs and TIMPs in CSF. MMP-2 mRNA levels in CSF WBCs were significantly up-regulated in comparison to PBMC expression levels, suggesting that MMP-2 is relevant for PBMC invasion into the subarachnoidal space and that the expression is influenced by migratory activity through the blood-CSF-barrier.
Assuntos
Doenças do Cão/enzimologia , Doenças do Cão/genética , Leucócitos Mononucleares/enzimologia , Metaloproteinase 2 da Matriz/genética , Meningite Asséptica/veterinária , Espaço Subaracnóideo/enzimologia , Corticosteroides/uso terapêutico , Animais , Barreira Hematoencefálica/enzimologia , Barreira Hematoencefálica/patologia , Doenças do Cão/tratamento farmacológico , Cães , Humanos , Leucócitos Mononucleares/patologia , Metaloproteinase 9 da Matriz/genética , Meningite Asséptica/tratamento farmacológico , Meningite Asséptica/enzimologia , Meningite Asséptica/genética , Neutrófilos/enzimologia , Neutrófilos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espaço Subaracnóideo/patologia , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Regulação para CimaAssuntos
Erros de Diagnóstico , Hibridização in Situ Fluorescente/métodos , Leucócitos Mononucleares/patologia , Meningite Asséptica/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Líquido Cefalorraquidiano/citologia , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core/líquido cefalorraquidiano , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Citodiagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Leucócitos Mononucleares/química , Meningite Asséptica/líquido cefalorraquidiano , Meningite Asséptica/genética , Proteínas de Fusão Oncogênica/líquido cefalorraquidiano , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RecidivaRESUMO
Mollaret's meningitis is a rare disease with a characteristic clinical course and distinctive cerebrospinal fluid (CSF) cytology. Although Mollaret originally described the large mononuclear cells seen in the CSF as endothelial, subsequent ultrastructural and immunocytochemical studies support a monocyte/macrophage lineage for these cells. To data, the pathogenesis of this entity remains uncertain, although an association with herpes simplex virus (HSV) has been reported in rare cases. In the current case study, immunocytochemistry for factor VIII-related antigen, leukocyte common antigen, and macrophage-specific antigen were performed and provide additional evidence of a monocyte/macrophage lineage for Mollaret cells. Polymerase chain reaction amplification for HSV DNA was done to further explore one possible etiology for this disease, but was negative.