RESUMEN
The aim of this research was to study cognitive dysfunctions in multiple sclerosis (MS) by exploring subtle cognitive tasks, usually not included in the standard neuropsychological assessment. We wished to investigate whether it is possible to identify object decision deficits in MS patients without evident cognitive impairment; secondary objectives were to understand whether these deficits can be detected in the early stages of the disease and whether there are differences related to different phenotypes. Participants were divided into four groups: (a) 12 patients with early relapsing-remitting MS [ERR]; (b) 14 with late relapsing-remitting MS [LRR]; (c) 10 with secondary progressive MS [SP]; (d) 36 healthy controls [HCs]. All participants performed a series of experimental tasks: an object decision task (recognition of chimeric and real figures) and naming and visual discrimination tasks. Our results suggest that object decision disorders are detectable in patients without overt cognitive impairments and that performances on these tasks are related to phenotypes. On the other hand, the Chimeric Figures task is not appropriate for identifying cognitive dysfunctions in early MS.
Asunto(s)
Disfunción Cognitiva/etiología , Toma de Decisiones/fisiología , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Adulto , Evaluación de la Discapacidad , Discriminación en Psicología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas Neuropsicológicas , Estimulación Luminosa , Aprendizaje Verbal , Adulto JovenAsunto(s)
Discriminación en Psicología , Potenciales Evocados Somatosensoriales , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/fisiopatología , Corteza Somatosensorial/fisiopatología , Adulto , Discriminación en Psicología/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
It has become evident that an autoimmune component could play a role in Alzheimer's disease (AD) onset and/or progression. The aim of this study was to identify neuronal antigenic targets specifically recognized by serum autoantibodies and to investigate their cellular effects and their possible pathogenetic role. We identified, by an immunoproteomic approach using mouse brain proteins, the adenosine triphosphate (ATP) synthase ß subunit as a new autoantigen in AD. Using an ELISA assay we found that serum anti-ATP synthase autoantibodies were present in 38% of patients with AD, but in no age-matched healthy subjects or in patients with Parkinson's disease or atherosclerosis. Analytical cytology studies, using SH-SY5Y neuroblastoma cell line, showed that ATP synthase autoantibodies were capable of inducing the inhibition of ATP synthesis, alterations of mitochondrial homeostasis and cell death by apoptosis. These findings suggest that autoantibodies specific to ATP synthase can exert a pathogenetic role via a mechanism that brings into play the impairment of the extracellular ATP homeostasis and the alteration of mitochondrial function triggering cell death by apoptosis.
Asunto(s)
Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/inmunología , Autoanticuerpos/sangre , ATPasas de Translocación de Protón Mitocondriales/inmunología , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/líquido cefalorraquídeo , Animales , Anexina A5/metabolismo , Apoptosis/efectos de los fármacos , Autoanticuerpos/farmacología , Encéfalo/metabolismo , Línea Celular Tumoral , Electroforesis en Gel Bidimensional , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Neuroblastoma/patología , Alineación de Secuencia , Factores de Tiempo , Adulto JovenRESUMEN
In this study, we report the case of a Chinese patient with systemic lupus erythematosus (SLE) who developed neutropenia after treatment by olanzapine for the SLE-related psychiatric symptoms. The relationship between agranulocytosis, SLE and olanzapine is still unknown. Fcγ receptor IIIb (FcγRIIIb) is a low-affinity receptor, constitutively expressed only by neutrophils; NA1 and NA2 have been identified as representing polymorphisms of FcγRIIIb. NA1 is associated with the incidence of autoimmune neutropenia and is particularly frequent in Asiatic ethnic groups. The Chinese patient resulted to be homozygous for NA1. We suggest that the presence of NA1 allele may be a predisposing factor to olanzapine-induced agranulocytosis in patients with SLE. Hence, the analysis of FcγRIIIb polymorphism should be investigated in other cases of antipsychotic-induced agranulocytosis.