Epstein-Barr Virus Load Correlates with Multiple Sclerosis-Associated Retrovirus Envelope Expression

pHERV-W ENV and syncytin-1, the envelope proteins of the human endogenous retrovirus W family (HERV-W), have been proposed as etiological factors for MS development. In addition, herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 6A/B (HHV-6A/B), have been also strongly associated with the disease. This work aims to study the possible link between viral loads and antibody titers against EBV and HHV-6A/B and the pHERV-W ENV/syncytin-1 protein/gene expression. For this purpose, we conducted a 12-month longitudinal study involving 98 RRMS patients. Peripheral blood samples were obtained from each patient. Serum antibody titers against EBV and HHV-6A/B were determined by ELISA, while viral loads were analyzed using qPCR. HLA MS-related alleles were also genotyped. pHERV-W ENV/syncytin-1 protein and gene expression levels in immune cells were assessed by flow cytometry and qPCR, respectively. We found that the 12-month variation of the pHERV-W ENV gene expression levels positively correlated with the variation of the EBV viral load, especially in those patients with high baseline EBV loads. Therefore, these results could support previous studies pointing to the transactivation of pHERV-W ENV by EBV. However, further studies are needed to better understand this possible relationship

Selenium status during pregnancy: Influential factors and effects on neuropsychological development among Spanish infants

Selenium (Se) has been positively associated with neurodevelopment in early life. However, its margin of safety is rather narrow, and few prospective studies have evaluated its potential neurotoxic effects at intermediate levels. We aimed to explore the association between maternal Se concentrations and child neuropsychological development, including the genetic effect modification of the Se metabolizing gene INMT. Study subjects were 650 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003–2005). Infant neuropsychological development was assessed around 12 months of age by the Bayley Scales of Infant Development. Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation. Se was measured in serum samples at the first trimester. The mean serum Se concentration was 79.7 (standard deviation = 7.9) μg/L. In multivariate analysis, nonsignificant inverse linear associations were found between Se concentrations and standardized mental and psychomotor development scores (β (95% CI) = − 0.13 (− 0.29, 0.03) and β (95% CI) = − 0.08 (− 0.24, 0.07), respectively). Generalized additive models indicated inverted U-shaped relationships between Se concentrations and both scales. Using segmented regression, the turning point for the associations was estimated at 86 μg/L for both scales. The association between Se and neuropsychological development was inverted U-shaped for children with the AG + AA genotype for rs6970396 INMT but a descending curve was suggested for the GG genotype. Further studies would be necessary in order to disentangle the complex equilibrium between the toxicity and benefits of Se exposure during the prenatal period

Solutions to Avoid False Positives for Rituximab in Pre-Transplant Crossmatches

Rituximab (anti-CD20) is commonly used as immunotherapy against B cells, in the context of pre-transplant crossmatches, where the presence of rituximab in the tested sera with donor cells can alter their results both by flow cytometry (FCXM) as complement-dependent cytotoxicity (CDCXM) giving rise to false positives. In the present study, we tested the use of an anti-rituximab monoclonal antibody (10C5, Abnova) as a method to avoid false positives in FCXM and CDCXM. We used the serum from ten patients who received therapy with rituximab, and the cells were incubated with sera treated or untreated with the 10C5 clone. In previous studies, attempts have been made to control these false positives through the use of pronase, although in these cases the alteration of Human Leukocyte Antigen (HLA) molecules has been found to be a limitation. As an alternative, we performed an assay to exclude false positives by a pre-incubation with anti-rituximab antibody (10C5) in 1:5 proportion avoiding the misinterpretation of crossmatches, particularly in patients with specific donor antibodies (DSA) without affecting the HLA molecules

Proceedings of 1 st HUMAINT workshop, Barcelona, Spain, March 5-6, 2018

[EN]This document contains the outcome of the first Human behaviour and machine intelligence (HUMAINT) workshop that took place 5-6 March 2018 in Barcelona, Spain. The workshop was organized in the context of a new research programme at the Centre for Advanced Studies, Joint Research Centre of the European Commission, which focuses on studying the potential impact of artificial intelligence on human behaviour. The workshop gathered an interdisciplinary group of experts to establish the state of the art research in the field and a list of future research challenges to be addressed on the topic of human and machine intelligence, algorithm's potential impact on human cognitive capabilities and decision making, and evaluation and regulation needs. The document is made of short position statements and identification of challenges provided by each expert, and incorporates the result of the discussions carried out during the workshop. In the conclusion section, we provide a list of emerging research topics and strategies to be addressed in the near future.Peer reviewe

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies

Altres ajuts: 2014 SGR 530 i 2009-SGR-159 de la Generalitat de Catalunya, Fundació Privada Cellex Barcelona i de l'Asociación Española Contra el CáncerBrain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasi

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population