Vocal markers of pre-operative anxiety: a pilot study

International audienceIntroduction Recent European guidelines in anaesthesia recommend systematic pre-operative anxiety management to prevent its negative peri-operative impact, 1 including impaired memorization of important instructions, and higher incidence of post-operative acute and chronic pain. Usual self-administered questionnaires or scales to assess anxiety in the preoperative setting are time-consuming and rely on the patients' willingness to comply with instructions. 2 Physiological signals such as patients' voice may provide useful information for objective, reliable, and accurate anxiety assessment before surgery. Because of the extensive parasympathetic innervation to the larynx, pharynx, face, and head, stress modifies vocal parameters. 3-4 The effects of acute anxiety on voice are poorly explored in the preoperative context. Our objective was to describe characteristics of patient's vocal parameters related to declared anxiety level in a day-care ophthalmic surgical unit performing cataract surgery

Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy

C3 glomerulopathy (C3G) results from acquired or genetic abnormalities in the complement alternative pathway (AP). C3G with monoclonal immunoglobulin (MIg-C3G) was recently included in the spectrum of “monoclonal gammopathy of renal significance.” However, mechanisms of complement dysregulation in MIg-C3G are not described and the pathogenic effect of the monoclonal immunoglobulin is not understood. The purpose of this study was to investigate the mechanisms of complement dysregulation in a cohort of 41 patients with MIg-C3G. Low C3 level and elevated sC5b-9, both biomarkers of C3 and C5 convertase activation, were present in 44 and 78% of patients, respectively. Rare pathogenic variants were identified in 2/28 (7%) tested patients suggesting that the disease is acquired in a large majority of patients. Anti-complement auto-antibodies were found in 20/41 (49%) patients, including anti-FH (17%), anti-CR1 (27%), anti-FI (5%) auto-antibodies, and C3 Nephritic Factor (7%) and were polyclonal in 77% of patients. Using cofactor assay, the regulation of the AP was altered in presence of purified IgG from 3/9 and 4/7 patients with anti-FH or anti-CR1 antibodies respectively. By using fluid and solid phase AP activation, we showed that total purified IgG of 22/34 (65%) MIg-C3G patients were able to enhance C3 convertase activity. In five documented cases, we showed that the C3 convertase enhancement was mostly due to the monoclonal immunoglobulin, thus paving the way for a new mechanism of complement dysregulation in C3G. All together the results highlight the contribution of both polyclonal and monoclonal Ig in MIg-C3G. They provide direct insights to treatment approaches and opened up a potential way to a personalized therapeutic strategy based on chemotherapy adapted to the B cell clone or immunosuppressive therapy

Revoir le dosage des sous-classes d'IgG. [Revisiting IgG subclass measurement.]

National audiencen.

A Fresh Perspective on Monoclonal Gammopathies of Renal Significance

International audienceMonoclonal gammopathies of renal significance (MGRS) encompass a remarkable variety of kidney diseases that result from intrinsic nephrotoxic properties of certain monoclonal Igs or their subunits. Effective disease-modifying treatments rely on the targeting of a malignant B-cell clone that may be demonstrable but often is quite hypothetical. Hence, convincing arguments for the genuine monoclonal character of the causative mono-isotypic Ig tissue deposits is needed for design of appropriate treatment strategies. The purpose of this article was to critically analyze distinct situations of suspected MGRS that occur in the practice of pathologists, nephrologists, hematologists, and immunologists. A particular focus of interest is the group of conditions known as proliferative glomerulonephritis with mono-isotypic immunoglobulin deposits (PGNMIDs), which illustrates the difficulties and ambiguities surrounding a definitive assignment of MGRS status

Maladies à prions

La longue période d’incubation des infections à prions offre une fenêtre pour une possible intervention thérapeutique avant l’atteinte irréversible et toujours fatale du système nerveux central. Cependant les événements physiopathologiques de ce stade asymptomatique sont encore mal compris. En particulier, alors que les sites anatomiques d’accumulation des prions sont bien identifiés, leurs modes de propagation dans l’organisme sont mal connus et apparemment complexes. Nous nous intéressons dans cet article à l’implication des cellules dendritiques comme vecteurs de ces agents. Grâce à des propriétés uniques d’exploration et de migration, les cellules dendritiques peuvent capturer les prions et faciliter leur propagation. Mais quelle est leur implication réelle dans la pathogenèse 

Subclass distribution of human myeloma proteins as determined with monoclonal antibodies.

International audienceSubclasses of 176 IgG and 62 IgA myeloma proteins were determined by indirect ELISA with monoclonal antibodies, as well as by an immunoblotting technique (for monoclonal IgG) and by immunoelectrophoresis against the lectin jacalin (for IgA). The subclass distribution of monoclonal IgG did not reflect mean normal serum levels of the correspondent isotypes, with an over-representation of IgG1 and IgG4 and an under-representation of IgG2 and IgG3 in myeloma. Similarly, IgA2 myeloma were clearly under-represented

Rôle des lymphocytes T CD4+ et des lymphocytes T régulateurs dans l immunothérapie et la physiopathologie de la maladie d Alzheimer (Etudes chez la souris)

L accumulation des peptides A 40-42 au niveau cérébral est un élément physiopathologique majeur de la Maladie d Alzheimer (MA) et une cible thérapeutique potentielle. A l issue de résultats encourageants de vaccination par A dans des modèles murins de la MA, un essai clinique a été entrepris chez l Homme. Mais il a dû être interrompu en raison de la survenue de méningo-encéphalites chez 6% des patients, supposées liées à une activation inappropriée de lymphocytes T. Une meilleure compréhension des réponses T CD4+ induites par la vaccination semble donc primordiale pour l optimisation des stratégies vaccinales. Nous avons cherché à identifier les facteurs génétiques qui pourraient avoir un rôle sur l amplitude et la nature des réponses vaccinales T CD4+ anti-A chez la souris. Nous avons mis en évidence que l amplitude de la réponse variait en fonction des haplotypes H-2 mais aussi de facteurs génétiques indépendants du CMH et liés à la capacité de générer des réponses T régulatrices (Tregs) anti-A . De plus, l analyse des réponses vaccinales dans un modèle murin de MA (souris APPPS1) semble suggérer qu une réponse Treg inhiberait des réponses T CD4 effectrices anti-A spontanées. Ces observations nous ont conduits à rechercher l impact de ces réponses effectrices et régulatrices dans la physiopathologie de la maladie. En inactivant les cellules Tregs, nous avons pu mettre en évidence les fonctions anti-neuroinflammatoires et les effets bénéfiques de ces cellules sur la pathologie amyloïde et la cognition. Ensemble, nos résultats suggèrent donc que les réponses Treg pourraient limiter l efficacité vaccinale mais auraient une action neuroprotectrice dans la physiopathologie de la MA.Cerebral accumulation of aggregated A 40-42 peptides is among the major pathological hallmarks of Alzheimer s disease (AD). In spite of encouraging results of A vaccination in preclinical mouse models, the first human clinical trial had to be interrupted because of the occurence of meningoencephalitides in 6% of the cases, supposedly related to inappropriate T cell responses. Thus, a better understanding of vaccination-induced anti-A CD4+ T cell responses seems essential for the optimisation of future immunotherapeutical approaches. We tried to identify the genetic factors that control the magnitude and the nature of vaccination-induced A -specific CD4+ T cell responses in mice. Both MHC-dependent and MHC-independent genetic factors are critical parameters. Among MHC-independent genetic factors, those that determine the individual propensity of generating A -specific regulatory T cell (Treg) responses are important. Moreover, the vaccination-induced CD4+ T cell responses analysis in an APPPS1 mouse model of AD suggest that Tregs may inhibit anti-A CD4+ T cells responses that spontaneously arise in the course of AD. These observations led us to evaluate the impact of CD4+ effector and regulatory T cell responses in the pathophysiology of AD. Using Treg depletion experiments, we evidenced the anti-neuroinflammatory functions and beneficial effects of these cells on the amyloid pathology and cognition of APPPS1 mice. Altogether, our results suggest that Treg responses may both limit vaccination efficacy and have a neuroprotective role in the course of AD.PARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF