Le syndrome lymphoprolifératif avec auto-immunité : Un défaut hérité ou acquis d’apoptose lymphocytaire

Le syndrome lymphoprolifératif avec auto-immunité (ALPS, auto-immune lymphoproliferative syndrome) a été décrit il y a plus de 30 ans. Ce syndrome tumoral bénin, d’apparition précoce (en moyenne avant cinq ans), associe des adénopathies multifocales, une splénomégalie et, éventuellement, une hépatomégalie. Cette lymphoprolifération chronique s’accompagne d’une hypergammaglobulinémie, essentiellement G et A, et se caractérise par l’accumulation dans le sang et les organes lymphoïdes secondaires d’une population polyclonale de lymphocytes Tαβ matures n’exprimant ni CD4 ni CD8, appelés lymphocytes T « doubles négatifs » (LTαβ DN). Des manifestations auto-immunes sont retrouvées chez plus de deux tiers des patients ALPS, le plus souvent sous la forme de cytopénies auto-immunes (anémie hémolytique, thrombopénie et neutropénie). Des atteintes d’organes ou de systèmes (glomérulonéphrites, hépatites, uvéites, syndrome de Guillain-Barré) sont plus rarement observées. Cet article fait le point sur les défauts de la voie de signalisation Fas mis en évidence dans la genèse de l’ALPS.Control of lymphocyte homeostasis is essential to ensure efficient immune responses and to prevent autoimmunity. Expansion followed by contraction of the lymphocyte pool are the basis of adaptive immune responses, and apoptosis is a crucial cellular modus operandi of the contraction phase. The death receptor Fas is a key player in lymphocyte apoptosis induction and patients lacking a functional Fas receptor develop a chronic lymphoproliferation termed autoimmune lymphoproliferative syndrome (ALPS). In rare instances, defects of the Fas signaling pathway have been associated with the ALPS condition. Although these defects with familial history are usually caused by inherited mutations of the corresponding genes, somatic mosaicism of these Fas mutations were also found in sporadic cases of ALPS. These findings might have important implications in deciphering the pathophysiological bases of other autoimmune diseases

Inferences from tip-calibrated phylogenies: a review and a practical guide

Molecular dating of phylogenetic trees is a growing discipline using sequence data to co-estimate the timing of evolutionary events and rates of molecular evolution. All molecular-dating methods require converting genetic divergence between sequences into absolute time. Historically, this could only be achieved by associating externally derived dates obtained from fossil or biogeographical evidence to internal nodes of the tree. In some cases, notably for fast-evolving genomes such as viruses and some bacteria, the time span over which samples were collected may cover a significant proportion of the time since they last shared a common ancestor. This situation allows phylogenetic trees to be calibrated by associating sampling dates directly to the sequences representing the tips (terminal nodes) of the tree. The increasing availability of genomic data from ancient DNA extends the applicability of such tip-based calibration to a variety of taxa including humans, extinct megafauna and various microorganisms which typically have a scarce fossil record. The development of statistical models accounting for heterogeneity in different aspects of the evolutionary process while accommodating very large data sets (e.g. whole genomes) has allowed using tip-dating methods to reach inferences on divergence times, substitution rates, past demography or the age of specific mutations on a variety of spatiotemporal scales. In this review, we summarize the current state of the art of tip dating, discuss some recent applications, highlight common pitfalls and provide a 'how to' guide to thoroughly perform such analyses

Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain

The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant TB in Argentina. We estimate that the progenitor of the outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by around 1973, indicating continuous circulation of a multidrug-resistant TB strain for four decades. By around 1979 the strain had acquired additional resistance to three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally.Fil: Eldholm, Vegard. Norwegian Institute of Public Health; NoruegaFil: Monteserin, Johana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rieux, Adrien. Colegio Universitario de Londres; Reino UnidoFil: Lopez, Beatriz. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Sobkowiak, Benjamin. Colegio Universitario de Londres; Reino UnidoFil: Ritacco, Gloria Viviana. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Balloux, Francois. Colegio Universitario de Londres; Reino Unid

Adaptive Discrete Laplace Operator

International audienceDiffusion processes capture information about the geometry of an object such as its curvature, symmetries and particular points. The evolution of the diffusion is governed by the Laplace-Beltrami operator which presides to the diffusion on the manifold. In this paper, we define a new discrete adaptive Laplacian for digital objects, gener- alizing the operator defined on meshes. We study its eigenvalues and eigenvectors recovering interesting geometrical informations. We discuss its convergence towards the usual Laplacian operator especially on lat- tice of diamonds. We extend this definition to 3D shapes. Finally we use this Laplacian in classical but adaptive denoising of pictures preserving zones of interest like thin structures