Estudio serológico del herpesvirus humano tipo 6 en pacientes con esclerosis múltiple

La Esclerosis Múltiple (EM) es una enfermedad inflamatoria crónica desmielinizante y neurodegenerativa que afecta selectivamente al Sistema Nervioso Central (SNC). Fundamentalmente se desarrolla en adultos jóvenes (25-30 años) y se caracteriza por la aparición de lesiones focales en la sustancia blanca (placas), en las que se puede observar desmielinización y destrucción axonal en grado variable con infiltración de gran número de células inflamatorias. En la formación y progresión de la lesión inflamatoria, participan tanto los linfocitos T, actuando sobre el parénquima cerebral tras atravesar la barrera hematoencefálica, como los linfocitos B, que contribuyen al proceso de desmielinización mediante la secreción de anticuerpos..

Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab

There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein–Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach

Herpesvirus Antibodies, Vitamin D and Short-Chain Fatty Acids: Their Correlation with Cell Subsets in Multiple Sclerosis Patients and Healthy Controls

Although the etiology of multiple sclerosis (MS) is still unknown, it is commonly accepted that environmental factors could contribute to the disease. The objective of this study was to analyze the humoral response to Epstein-Barr virus, human herpesvirus 6A/B and cytomegalovirus, and the levels of 25-hydroxyvitamin D (25(OH)D) and the three main short-chain fatty acids (SCFA), propionate (PA), butyrate (BA) and acetate (AA), in MS patients and healthy controls (HC) to understand how they could contribute to the pathogenesis of the disease. With this purpose, we analyzed the correlations among them and with different clinical variables and a wide panel of cell subsets. We found statistically significant differences for most of the environmental factors analyzed when we compared MS patients and HC, supporting their possible involvement in the disease. The strongest correlations with the clinical variables and the cell subsets analyzed were found for 25(OH)D and SCFAs levels. A correlation was also found between 25(OH)D and PA/AA ratio, and the interaction between these factors negatively correlated with interleukin 17 (IL-17)-producing CD4+ and CD8+ T cells in untreated MS patients. Therapies that simultaneously increase vitamin D levels and modify the proportion of SCFA could be evaluated in the future

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

Relación entre la cuantificación de calcio coronario y la composición de la microbiota intestinal en sujetos sin enfermedad cardiovascular previa: estudio piloto

[Aim]: To investigate the relationship between gut microbiota composition and the presence of coronary atherosclerosis assessed by coronary artery calcium (CAC) quantification in individuals without previous cardiovascular disease (CVD). [Methods]: We included 20 patients over 18 years of age with no history of CVD who underwent multiple detector-computed tomography. From each patient, a stool sample was obtained to characterize gut microbiota composition by sequencing bacterial 16S ribosomal RNA gene. In addition, circulating levels of TNF-α and IL-1β, as well as trimethylamine N-oxide (TMAO) were determined in plasma samples by automated ELISA and capillary gas chromatography-mass spectrometry, respectively. [Results]: The mean age of patients was 63.5 years and 60% were women. Half of patients had CAC >100 (Agatston score), and were characterized by a higher abundance of the phylum Proteobacteria, mainly of bacteria belonging to the families Enterobacteriaceae and than patients with a CAC ≤ 100. Moreover, bacterial genera identified as biomarkers, such as Enterobacter, Escherichia/Shigella y Klebsiella, were positively associated with inflammation levels and with TMAO production. [Conclusion]: Our data shows a gut microbiota profile associated with the presence of coronary calcium in patients without previous CVD. Although there are no strategies to decrease the amount of coronary calcium, gut microbiota is highly malleable by several factors. The possibility of preventing and even intervening CVD progression through strategies targeted gut microbiota is a very attractive idea that deserves further studies.[Objetivo]: Determinar si existe alguna asociación entre el perfil de microbiota intestinal y la carga aterosclerótica global medida mediante cuantificación de calcio coronario (CCC) en sujetos sin antecedentes de enfermedad cardiovascular (ECV). [Métodos]: Se incluyeron 20 pacientes mayores de edad, sin antecedentes de ECV a los que se les hizo la CCC mediante tomografía computarizada multicorte. Además, se les recogió una muestra de heces para caracterizar la composición de la microbiota intestinal mediante la secuenciación del gen 16S RNAr con técnicas de secuenciación masiva y una muestra de sangre para la cuantificación de citoquinas proinflamatorias, mediante ELISA específicos, y del metabolito bacteriano N-óxido de trimetilamina (TMAO) por cromatografía de gases/líquidos acoplada a espectrometría de masas en tándem. [Resultados]: La media de edad fue de 63,5 años y un 60% eran mujeres. La mitad de los pacientes (n = 10) presentaron una CCC >100 y se caracterizaron por una mayor abundancia de bacterias del filo Proteobacteria, pertenecientes principalmente a las familias Enterobacteriaceae y Pasteurellaceae, que los pacientes con CCC ≤ 100. La mayoría de los géneros bacterianos identificados, Enterobacter, Escherichia/Shigella, Klebsiella, Citrobacter y Salmonella, se asociaron positivamente con los niveles plasmáticos de TNF-α o IL-1β y con la producción de TMAO. [Conclusión]: Los resultados de este estudio piloto muestran un perfil de microbiota intestinal asociado a la presencia de CCC >100 en pacientes sin ECV previa, caracterizado por un aumento en la proporción de géneros bacterianos productores de TMAO. Puesto que la composición de la microbiota intestinal es altamente modulable por diversos factores, es posible que, en un futuro, podamos prevenir, e incluso intervenir, la enfermedad cardiovascular mediante estrategias nutricionales.Este trabajo ha sido parcialmente financiado con una Beca Fundación Española de Arteriosclerosis (FEA)/Sociedad Española de Arteriosclerosis (SEA) 2016 para Investigación Básica, concedida durante el XXIX Congreso Nacional SEA celebrado en Granada del 18 al 20 de mayo de 2016

Clinical and demographic characteristics of the samples and subjects included in the study.

<p>*At least two-years of follow-up with the same disease modifying therapy (DMT) from a base line visit (serum sample extracted before starting the DMT) to a 24 months visit.</p><p>**EDSS: Expanded Disability Status Scale. MSSS: Multiple Sclerosis Severity Score.</p><p>***It was included: adverse events, pregnancy, drug withdrawal for lack of efficacy, and patient decision.</p

Anti-HHV-6A/B IgG and IgM titers in 216 serum samples collected in relapse (REL.) and in 278 serum samples collected three months before and after the relapse (n = 21 at day–84, n = 20 at day –70, n = 23 at day –56, n = 23 at day –42, n = 25 at day –28, n = 31 at day –14, n = 26 at day 14, n = 21 at day 28, n = 22 at day 42, n = 24 at day 56, n = 23 at day 70, n = 19 at day 84).

<p>A. Anti-HHV-6A/B IgG response. B. Anti-HHV-6A/B IgM response.</p