Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Immune system. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)

Abstract: Objectives Treat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. Methods An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. Results The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions: 1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs). 2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician9s global assessment. 3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics. The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. Conclusions The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.

Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels

Abstract: Uncovering principles that regulate energy metabolism in the brain requires mapping of partial pressure of oxygen (PO(2)) and blood flow with high spatial and temporal resolution. Using two-photon phosphorescence lifetime microscopy (2PLM) and the oxygen probe PtP-C343, we show that PO(2) can be accurately measured in the brain at depths up to 300 μm with micron-scale resolution. In addition, 2PLM allowed simultaneous measurements of blood flow and of PO(2) in capillaries with less than one-second temporal resolution. Using this approach, we detected erythrocyte-associated transients (EATs) in oxygen in the rat olfactory bulb and showed the existence of diffusion-based arterio-venous shunts. Sensory stimulation evoked functional hyperemia, accompanied by an increase in PO(2) in capillaries and by a biphasic PO(2) response in the neuropil, consisting of an 'initial dip' and a rebound. 2PLM of PO(2) opens new avenues for studies of brain metabolism and blood flow regulation.

Gene × Environment interactions in autism spectrum disorders: role of epigenetic mechanisms.

Abstract: Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD). First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene X environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of in utero exposure to valproate provides a good illustration of epigenetic mechanisms involved in ASD and innovative therapeutic strategies. Epigenetic remodeling by environmental factors opens new perspectives for a better understanding, prevention and early therapeutic intervention of ASD.

High Incidence of NLRP3 Somatic Mosaicism in Patients With Chronic Infantile Neurologic, Cutaneous, Articular Syndrome: Results of an International Multicenter Collaborative Study

Abstract: Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome (MIM no. #607715), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a dominantly-inherited autoinflammatory disease that is characterized by neonatal onset and the triad of urticarial-like skin rash, neurologic manifestations, and arthritis/arthropathy. Patients often experience recurrent fever and systemic inflammation. NOMID/CINCA syndrome is the most severe clinical phenotype of the cryopyrin-associated periodic syndromes (CAPS) that also include the 2 less severe but phenotypically similar syndromes familial cold autoinflammatory syndrome (FCAS; MIM no. #120100) and Muckle-Wells syndrome (MIM no. #191900). CAPS are caused by mutations in the NLRP3 gene, which is a member of the nucleotide-binding oligomerization domain–like receptor (NLR) family of the innate immune system (1, 2). NLRP3 is an intracellular “sensor” of danger signals arising from cellular insults, such as infection, tissue damage, and metabolic deregulation, and it has been highly conserved throughout evolution. NLRP3 associates with ASC and procaspase 1 to constitute a large multiprotein complex termed the NLRP3 inflammasome. When activated, the NLRP3 inflammasome converts the biologically inactive procaspase 1 into active caspase 1. Caspase 1 produces the cytokines interleukin-1β (IL-1β) and IL-18, which are mainly involved in the inflammatory response (3). Available research suggests that mutated NLRP3 induces autoactivation of the NLRP3 inflammasome in CAPS patients, resulting in an uncontrolled overproduction of IL-1β. Most CAPS patients carry heterozygous germline missense mutations in the NLRP3 coding region (“mutation-positive” patients) (4, 5). More than 80 different disease-causing mutations have been reported to date (6). However, ~40% of clinically diagnosed NOMID/CINCA syndrome patients show no heterozygous germline NLRP3 mutation during conventional Sanger-sequencing-based genetic analyses (“mutation-negative” patients). Comparisons of NOMID/CINCA syndrome patients with and without heterozygous germline NLRP3 mutations have revealed no differences in clinical features or response to treatment (4, 7). In a previous study, we identified a high incidence of somatic NLRP3 mosaicism in “mutation-negative” NOMID/CINCA syndrome patients in Japan (8). We therefore hypothesized that somatic NLRP3 mosaicism may be implicated in the etiology of the disorder, although its precise contribution remains unclear. The aim of the present study was to evaluate both the frequency of NLRP3 somatic mosaicism in NOMID/CINCA syndrome patients and the association between somatic mosaicism and clinical phenotype using an international cohort of mutation-negative NOMID/CINCA syndrome patients.