RESUMEN
Neuromyelitis optica (NMO), an uncommon central nervous system (CNS) demyelinating disease, produces transverse myelitis and severe optic neuritis. IgG-NMO autoantibody, a specific immunoglobulin binding aquaporin-4 water channel protein, confirms that NMO is a different entity to multiple sclerosis. Parallel to cytokine down-regulations found in serum of relapsing-NMO (rNMO) patients, it has been reported that IgG-NMO may also confer a worse course of the disease in r-NMO Caribbean patients. In this study, we were interested in exploring the influence of IgG-NMO autoantibody on S100beta levels and clinical parameters from serum of r-NMO patients. Serum samples from 24 rNMO patients and 10 controls were evaluated. The reduction of S100beta observed in r-NMO patients was not significant compared to controls; and no differences were present regarding IgG-NMO immunoreactivity. At the same time, a significant correlation was also observed between IgG-NMO autoantibody serum detection and EDSS (Expanded Disability Status Scale) in rNMO. These results corroborate a differential regulation of IgG-NMO autoantibodies on the S100beta glial marker and on the disability present in rNMO patients.
Asunto(s)
Acuaporina 4/inmunología , Autoanticuerpos/sangre , Inmunoglobulina G/sangre , Factores de Crecimiento Nervioso/sangre , Neuromielitis Óptica/sangre , Neuromielitis Óptica/inmunología , Proteínas S100/sangre , Adulto , Biomarcadores/análisis , Biomarcadores/sangre , Evaluación de la Discapacidad , Regulación hacia Abajo/inmunología , Femenino , Humanos , Inmunomodulación/fisiología , Masculino , Persona de Mediana Edad , Factores de Crecimiento Nervioso/análisis , Neuromielitis Óptica/fisiopatología , Recurrencia , Subunidad beta de la Proteína de Unión al Calcio S100 , Proteínas S100/análisisRESUMEN
ABSTRACT: BACKGROUND: Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress. METHODS: We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-alpha, IFN-gamma, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured. RESULTS: We found almost undetectable levels of TNF-alpha, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-alpha and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector - regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship. CONCLUSION: These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis(AU)
Asunto(s)
Humanos , Factor de Necrosis Tumoral alfa/sangre , Neuromielitis Óptica/inmunología , Estrés OxidativoRESUMEN
BACKGROUND: Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress. METHODS: We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-alpha, IFN-gamma, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured. RESULTS: We found almost undetectable levels of TNF-alpha, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-alpha and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector - regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship. CONCLUSION: These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis.