Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Type I interferon-mediated autoinflammation due to DNase II deficiency

Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans

Lymphopénie CD4 tardive chez le transplanté rénal

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Anti-MuSK positivity on plasmapheresis liquid in a double seronegative myasthenia gravis patient

International audienc

Restricted specificity of peripheral alloreactive memory B cells in HLA-sensitized patients awaiting a kidney transplant

International audienceThe contribution of memory B cells in alloreactive humoralresponses remains poorly understood. Here we testedthe presence of circulating alloreactive memory B cells in69 patients with end-stage renal disease under renalreplacement therapy, using an in vitro memory Bcell–stimulation assay combined with identification of IgGhuman leukocyte antigen (HLA) antibodies in culturesupernatant. HLA antibody–producing memory B cells wereevidenced only in patients carrying serum HLA antibodiesfollowing multiple classical HLA-immunizing events. Inpatients with a previous renal allograft, alloreactive memoryB cells could be detected ranging from 6 to 32 years (mean13.2 years) after transplantation. HLA antibodies produced bymemory B cells were also detected in the corresponding seraand showed a restricted reactivity, targeting only a fewepitopes shared by several HLA antigens. In contrast, serumHLA antibodies, not associated with the detection of specificmemory B cells, showed a broader pattern of specificities.Thus, expansion and survival of alloreactive memory B cells isalloantigen driven, and their frequency is related to the‘strength’ of HLA immunization

Regulatory mechanisms of immune tolerance in type 1 diabetes and their failures

International audienc

Understanding Pathogenesis and Care Challenges of Immune Reconstitution Inflammatory Syndrome in Fungal Infections

International audienceImmune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRI

Chronic Disseminated Candidiasis During Hematological Maligancies: An Immune Reconstitution Inflammatory Syndrome with Expansion of Pathogen-Specific TH1 T Cells

International audienceChronic disseminated candidiasis (CDC) is a rare disease mostly occurring after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease. To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls (CANHPARI NCT01916057). Analysis of Candida-specific T cell responses using Elispot assays revealed higher numbers of IFNγ-producing T cells reactive to mp65 or candidin in 27 CDC cases as compared to 33 controls. Increased plasma levels of sCD25, IL-6, IL-1β, TNFα and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher level of CD4 and CD8 T cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCRγδ+Vδ2+ cells. The expansion of Candida-specific IFNγ-producing T cells together with features of T cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes (IRIS)