RESUMEN
The TNF superfamily ligand, TNF-like weak inducer of apoptosis (TWEAK), regulates cellular responses ranging from proliferation to cell death in a manner highly dependent on the cell type and the microenvironmental context. We have shown previously that treatment of experimental autoimmune encephalomyelitis mice after the priming phase with neutralizing anti-TWEAK antibodies results in a reduction in the severity of the disease and leukocyte infiltration. To further characterize TWEAK/fibroblast growth factor-inducible 14-kDa protein (Fn14) involvement during multiple sclerosis (MS), we evaluated in MS patients and controls: TWEAK and Fn14 expression on PBMC and soluble TWEAK concentration in serum and cerebrospinal fluid (CSF). Thirty-six consecutive patients were enrolled, including 11 patients with relapsing-remitting MS, 11 with a clinical isolated syndrome suggestive of MS (CISSMS), and 14 controls with non-MS diseases. Intracellular TWEAK could be observed in lymphocytes and/or monocytes in all groups of patients. None of the 36 patients displayed TWEAK expression at the cell surface of lymphocytes. In contrast, 12 out of the 36 patients were positive for membrane TWEAK expression on their monocytes. Among these patients, eight were from the CISSMS group. Fn14 was not detected in PBMC. The soluble form of TWEAK is detectable in serum and CSF of patients, and TWEAK concentrations were not statistically different between the disease groups. We demonstrated for the first time that TWEAK is expressed at the cell surface of monocytes during MS, especially in the CISSMS group. Our results support the proposal that TWEAK could be a target for antibody therapy in MS.
Asunto(s)
Membrana Celular/metabolismo , Monocitos/metabolismo , Esclerosis Múltiple/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Factores de Necrosis Tumoral/biosíntesis , Adolescente , Adulto , Anciano , Citocina TWEAK , Femenino , Humanos , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Receptor de TWEAK , Factores de Necrosis Tumoral/sangre , Factores de Necrosis Tumoral/líquido cefalorraquídeo , Adulto JovenAsunto(s)
Clorobencenos/envenenamiento , Enfermedades en Gemelos , Erupciones por Medicamentos/etiología , Repelentes de Insectos/envenenamiento , Síndromes de Neurotoxicidad/etiología , Trastornos Relacionados con Sustancias/complicaciones , Adolescente , Femenino , Humanos , Ictiosis/inducido químicamente , Trastornos Relacionados con Sustancias/diagnósticoAsunto(s)
Hidrocefalia/diagnóstico por imagen , Adulto , Humanos , Hidrocefalia/cirugía , Masculino , Cintigrafía , VentriculostomíaAsunto(s)
Infarto Cerebral/etiología , Glucocorticoides/efectos adversos , Inmunoglobulinas Intravenosas/efectos adversos , Metilprednisolona/efectos adversos , Quimioterapia Combinada , Femenino , Glucocorticoides/administración & dosificación , Humanos , Metilprednisolona/administración & dosificación , Persona de Mediana EdadAsunto(s)
Inmunoglobulinas Intravenosas/efectos adversos , Metilprednisolona/efectos adversos , Trombosis de la Vena/inducido químicamente , Adulto , Quimioterapia Combinada , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/etiologíaRESUMEN
Oligoclonal free light chains (FLC) banding has been described in multiple sclerosis (MS) and should be correlated with disease activity. However, discrepancies between studies have been reported because of differences in methods. A new quantitative, rapid, and automated method using nephelometry is now available. Our objective was to investigate the interest of this method for the diagnosis and prognosis of MS. For this purpose, FLC index was determined in paired samples of CSF and serum from consecutive and unselected patients from the same department of neurology. We enrolled 89 patients (33 MS, 15 "possible MS", and 41 controls) and correlated with IgG index, IgG oligoclonal banding, and clinical MS progression criteria. The main results were (1) FLC kappa index was more sensitive but less specific than IgG index for the diagnosis of MS, (2) two MS patients were negative for oligoclonal banding but exhibited a positive kappa index, (3) no relation between FLC kappa indices, MS clinical criteria, and disease progression was found. In conclusion, FLC kappa index should be considered as a useful complementary test for MS diagnosis. Its pronostic interest remains to be determined on a larger cohort of possible MS patients.
Asunto(s)
Cadenas Ligeras de Inmunoglobulina/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Nefelometría y Turbidimetría , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Inmunoensayo/métodos , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Cadenas Ligeras de Inmunoglobulina/sangre , Cadenas kappa de Inmunoglobulina/sangre , Cadenas kappa de Inmunoglobulina/líquido cefalorraquídeo , Cadenas lambda de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Nefelometría y Turbidimetría/métodos , Sensibilidad y EspecificidadRESUMEN
A 45-year-old man with a cholesteatoma experienced purulent meningitis. Microbial analysis of cerebrospinal fluid yielded in pure culture a gram-negative bacillus. Phenotypic methods were suggestive of a Bacteroides distasonis or either a Bacteroides thetaiotaomicron or Bacteroides ovatus infection. The isolate was identified by 16S rRNA gene sequence analysis as B. thetaiotaomicron. This is the first case of B. thetaiotaomicron meningitis in pure culture.