Éditeur(s) : HAL CCSD
Résumé : National audience
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis and detecting PAH efficiently remains challenging. The DETECT study has offered in 2013 a composite screening tool for PAH. The objective of our study was to compare the indication of right heart catheterisation (RHC) as suggested by the DETECT algorithm with the decisions of a multidisciplinary team. METHODS: This prospective monocentric non-interventional study consecutively included systemic sclerosis patients when data required to apply DETECT algorithm were available. We evaluate the number of RHC as requested by this algorithm and confronted it with the indications of RHC suggested by a multidisciplinary group blinded for the result of DETECT algorithm. RESULTS: In total, 117 systemic sclerosis patients were included. When DETECT algorithm was applied to all patients, RHC was suggested by this algorithm for 70 patients, whereas only 15 indications were required by the multidisciplinary group; among those patients only 7 had PAH. When DETECT algorithm was applied only to the 42 patients with DLCO<60% and disease duration of more than 3 years, RHC was suggested for 31 patients whereas only 13 were indicated by the multidisciplinary group; among those patients only 7 had PAH. CONCLUSION: The DETECT algorithm is able to efficiently detect all PAH patients finally diagnosed by our multidisciplinary team. However, it increases by 3 the number of RHC that should be performed.
La Revue de Médecine Interne

hal-01579606
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579606
DOI : 10.1016/j.revmed.2017.04.005
PUBMED : 28545856

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (+/- 0.034) vs HD 0.039 Giga/L (+/- 0.030), p < 0.01, and dSSc 0.071 Giga/L (+/- 0.034) vs lSSc 0.048 Giga/L (+/- 0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.
ISSN: 0770-3198

hal-01560150
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560150
DOI : 10.1007/s10067-017-3597-6
PUBMED : 28293753

Résumé : Les pathologies inflammatoires démyélinisantes primitives du système nerveux central (SNC) sont dominées par deux entités : la sclérose en plaques (SEP) et la neuromyélite optique (NMO). Ces deux pathologies se différencient par : 1. leur phénotype, la NMO se caractérisant par une myélite extensive dans le plan transversal et longitudinal et peu de lésions encéphaliques initiales ; 2. leur sévérité, le pronostic de la NMO étant moins bon que celui de la SEP ; 3. leur mécanisme immunologique, puisque l’immunité humorale domine nettement dans la NMO, cette pathologie répondant peu ou pas aux traitementshabituellement prescrits dans la SEP. Un anticorps sérique (IgG-NMO) a été retrouvé chez les patients atteints de NMO avec une sensibilité de 50-70% et une spécificité de 90-100%. Cet anticorps a pour cible le principal canal hydrique du SNC, l’aquaporine-4 (AQP4), qui se situe principalement sur les pieds astrocytaires jalonnant la barrière hémato-encéphalique. La SEP est relativement familière des neurologues car décrite sur le plan épidémiologique et dans son histoire naturelle depuis plus d’un siècle à travers de larges séries réalisées parfois en population générale. Son approche thérapeutique progresse suite à des essais contrôlés qui s’accumulent depuis maintenant près de 20 ans. Toutefois, la majorité des travaux ont été effectués chez les populations Caucasiennes en raison de sa plus grande fréquence dans ces populations. A l’inverse, la NMO garde encore un relatif mystère à cause de sa relative rareté, l’établissement très récent de critères diagnostiques et une physiopathologie très récemment éclaircie par la découverte de l’IgG-NMO qui a indiscutablement suscité un regain d’intérêt de cette affection. Ainsi, son incidence est quasiment inconnue de même que sa susceptibilité génétique. La progression du handicap de la NMO qu’il soit visuel ou moteur à l’évidence sévère, ne repose toujours pas sur des chiffres précis, la description des lésions neuroradiologiques reste encore très embryonnaire. Enfin, même s’il existe un consensus pour traiter énergiquement les poussées de NMO et les espacer, il n’existe quasiment aucune étude prospective.
Introduction: Aim of the study is to describe épidemiology, phenotype and treatment of demyelinating inflammatory diseases of the central nervous system (CNS) namely multiple sclerosis (MS) and neuromyelitis optica (NMO) in French West Indies.Epidemiology: MS emerged in the French West Indian (FWI) population with an incidence of 1.27/100 000 (CI 95%: 1.16-1.38) for the period 1992-2007 while incidence of NMO remained stable at 0.19/100,000 (CI 95%: 0.15–0.23). Both migration in Metropolitean France (MF) and decrease of sun exposure were risk factors for MS acquisition in FWI. Phenotype and treatment of NMO: NMO is a very rapidly disabling disease with median times to reach DSS 3, 6 and 8 of one year, 8 years and 22 years respectively. However, treatment by plasma exchanges were shown to reduce sequellae of NMO attacks ; mitoxantrone and rituximab reduced significantly annualized relapse rate (ARR) from 1.7 to 0.29 (p<10-4) and from 1,34 to 0,56 (p=0.0005) respectively, improving dramatically natural course of NMO.Phenotype and treatment of MS: Absence of Migration in MF in MS patients was found to be the strongest independent predictive factor of disability progression to DSS 6 (hazard ratio, 2.59; p=0.0002); beside short time to DSS3 (p=0.005), later age at onset (p=0.005), and multi-symptomatic onset (p=0.03). Treatment of MS by interferon beta-1 had a moderate impact in MS while natalizimab proved to be highly effective by reducing drastically ARR and inflammatory parameters on magnetic resonance imaging. Conclusion: Spectrum of demyelinating inflammatory disorders of CNS has reversed in French West Indies with overrepresentation of MS. Agressive therapy is needed to improve prognosis of NMO. Rapidly increasing of its incidence makes MS a new public health problem in French West Indies.

http://www.theses.fr/2012AGUY0511/document

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The cyanobacteria-derived neurotoxin β-methylamino-l-alanine (BMAA) represents a plausible environmental trigger for amyotrophic lateral sclerosis (ALS), a debilitating and fatal neuromuscular disease. With the eutrophication of water bodies, cyanobacterial blooms and their toxins are becoming increasingly prevalent in France, especially in the Brittany region. Cyanobacteria are monitored at only a few recreational sites, preventing an estimation of exposure of the human population. By contrast, phosphorus, a limiting nutrient for cyanobacterial growth and thus considered a good proxy for cyanobacteria exposure, is monitored in many but not all surface water bodies. Our goal was to develop a geographic exposure indicator that could be used in epidemiological research. We considered the total phosphorus (TP) concentration (mg/L) of samples collected between October 2007 and September 2012 at 179 monitoring stations distributed throughout the Brittany region. Using readily available spatial data, we computed environmental descriptors at the watershed level with a Geographic Information System. Then, these descriptors were introduced into a backward stepwise linear regression model to predict the median TP concentration in unmonitored surface water bodies. TP concentrations in surface water follow an increasing gradient from West to East and inland to coast. The empirical concentration model included five predictor variables with a fair coefficient of determination (R2 = 0.51). The specific total runoff and the watershed slope correlated negatively with the TP concentrations (p = 0.01 and p < 10− 9, respectively), whereas positive associations were found for the proportion of built-up area, the upstream presence of sewage treatment plants, and the algae volume as indicated by the Landsat red/green reflectance ratio (p < 0.01, p < 10− 6 and p < 0.01, respectively). Complementing the monitoring networks, this geographical modeling can help estimate TP concentrations at the watershed level, delivering a proxy for cyanobacteria exposure that can be used along with other risk factors in further ALS epidemiologic case–control studies
ISSN: 0160-4120

hal-01175538
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01175538
DOI : 10.1016/j.envint.2015.04.007
PUBMED : 25913322

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Coronaviruses (CoVs) have shown neuroinvasive properties in human and animal secondary to replication in peripheral organ but the mechanism of neuroinvasion is unknown. The major aim of our work was to evaluate the ability of CoVs to enter the central nervous system (CNS) through the blood brain barrier (BBB). Using the high hepatotropic mouse hepatitis virus (MHV) type 3, its attenuated variant 51.6-MHV3, showing low tropism for endothelial cells, and the low hepatotropic MHV-A59 strains from murine coronavirus group, we investigated the viral-induced dysfunctions of BBB in vivo and in brain microvascular endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability to cross the BBB during acute infection according to their virulence for liver. Brain invasion was only observed in MHV3-infected mice and correlated with enhanced BBB permeability associated with decreased expression of ZO-1, VE-cadherin and occludin but not claudin-5 in the brain or in cultured BMECs. BBB breakdown in MHV3 infection was not related to production of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs but rather to a downregulation of barrier protective IFN-β production. Our findings highlight the importance of IFN-β production by infected BMECs in preserving BBB function and preventing access of blood-borne infectious viruses to the brain. IMPORTANCE: Coronaviruses (CoVs) infect several mammals including humans and are associated with respiratory, gastrointestinal and/or neurological diseases. Some evidences suggest that human respiratory CoVs may show neuroinvasive properties. Indeed, the SARS-CoV, causing severe acute respiratory syndrome, and the CoVs OC43 and 229E were found in the brains of SARS and multiple sclerosis patients respectively. These finding suggest that hematogenous spread CoVs may gain access to CNS at the BBB level. Herein we report for the first time that CoVs exhibit ability to cross the BBB according to strain virulence. BBB invasion by CoVs correlates with viral-induced disruption of tight junctions on BMECs, leading to BBB dysfunction and enhanced permeability. We provide evidence that production of IFN-β by BMECs during CoV infection may prevent BBB breakdown and brain viral invasion
ISSN: 0022-538X

hal-01187308
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187308
DOI : 10.1128/JVI.01501-15
PUBMED : 26202229