Caractéristiques et modalités évolutives de l' anémie hémolyotique auto-immune à anticorps chauds de l' adulte (série rétrospective monocentrique de 60 patients)

Nous avons mené une étude rétrospective monocentrique sur l anémie hémolytique auto-immune à anticorps chauds de l adulte, incluant 60 patients d âge moyen 54+-23 ans. L AHAI était considérée comme primitive dans 35% des cas. Les formes secondaires étaient le plus souvent liées à une hémopathie lymphoïde (23%) ou une autre maladie auto-immune (13%). La quasi-totalité des patients a reçu une corticothérapie avec 87% de réponse initiale mais une cortico-dépendance dans 63% des cas, nécessitant une seconde ligne de traitement chez 52% des patients. Une réponse complète à la corticothérapie était prédictive de rémission en fin de suivi. Au total, 45% ont reçu du rituximab, avec 86% de réponse initiale mais des rechutes fréquentes. La splénectomie était réalisée chez 8 patients avec dans tous les cas une réponse initiale, mais durable que chez la moitié. Au total, après un suivi de 42+-40 mois, 52% des patients étaient en rémission complète (absence d hémolyse en l absence de traitement poursuivi) et 20% en rémission partielle. Pour les 28% restants, l AHAIc était toujours active (hémolyse non compensée et/ou nécessité de poursuivre un traitement autre qu une corticothérapie inférieure à 10mg/j d équivalent prednisone). Dix patients (17%) ont présenté des manifestations thrombo-emboliques veineuses, 5 patients (8%) sont décédés. La comparaison de l ensemble des formes secondaires aux formes primaires n a pas montré de différence significative. En revanche, dans le sous-groupe des AHAIc associées à une hémopathie lymphoïde, une hypogammaglobulinémie et surtout une immunoglobuline monoclonale étaient plus fréquemment observées et la réponse à la corticothérapie était moins bonne.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan

Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer’s and Parkinson’s). Taking into account the recent identification of microglia-specific markers, and the availability of compounds that target these cells selectively in vivo, we consider the prospect of disease intervention via the microglial route

Combinatorial Control of Th17 and Th1 Cell Functions by Genetic Variations in Genes Associated With the Interleukin-23 Signaling Pathway in Spondyloarthritis

International audienceRecent genome-wide association studies have revealed numerous genetic associations between specific single-nucleotide polymorphisms (SNPs) and immune-mediated inflammatory diseases. The current challenge is to identify associations of the genetic variants with effector mechanisms implicated in pathogenesis. This study was undertaken to investigate the link between genetic variation at loci associated with spondyloarthritis (SpA) and the effector function of CD4+ T lymphocyte subsets involved in chronic inflammatory disease

Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan

International audienceMicroglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia-specific markers, and the availability of compounds that target these cells selectively in vivo, we consider the prospect of disease intervention via the microglial route

Effet d’un traitement par hydroxychloroquine prescrit comme traitement de fond de rhumatismes inflammatoires chroniques ou maladies auto-immunes systémiques sur les tests diagnostiques et l’évolution de l’infection à SARS CoV-2: étude de 871 patients

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Impact of hydroxychloroquine used as DMARD on SARS-CoV-2 tests and infection evolution in a population of 871 patients with inflammatory rheumatic and musculoskeletal diseases

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High dose romiplostim as a rescue therapy for adults with severe bleeding and refractory immune thrombocytopenia

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Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants

International audienceAlthough tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment. The plasma of both treated and non-treated patients infected with the ancestral variant exhibit strong neutralizing activity against the ancestral virus and the Alpha, Beta, and Delta variants of SARS-CoV-2, whereas the Gamma and Omicron viruses were less sensitive to seroneutralization. Overall, we observed that, despite the clinical benefits of short-term tocilizumab therapy in modifying the cytokine storm associated with COVID-19 infections, there were no modifications in the robustness of B cell and IgG responses to Spike antigens

Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine.

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Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis

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