Toward a Better Classification System for NK-LGL Disorders

International audienceLarge granular lymphocytic leukemia is a rare lymphoproliferative disorder characterized by a clonal expansion of T-lineage lymphocyte or natural killer (NK) cells in 85 and 15% of cases respectively. T and NK large granular leukemia share common pathophysiology, clinical and biological presentation. The disease is characterized by cytopenia and a frequent association with autoimmune manifestations. Despite an indolent course allowing a watch and wait attitude in the majority of patients at diagnosis, two third of the patient will eventually need a treatment during the course of the disease. Unlike T lymphocyte, NK cells do not express T cell receptor making the proof of clonality difficult. Indeed, the distinction between clonal and reactive NK-cell expansion observed in several situations such as autoimmune diseases and viral infections is challenging. Advances in our understanding of the pathogenesis with the recent identification of recurrent mutations provide new tools to prove the clonality. In this review, we will discuss the pathophysiology of NK large granular leukemia, the recent advances in the diagnosis and therapeutic strategies

Prolonged thrombocytopenia after CAR T-cell therapy: the role of thrombopoietin receptor agonists

International audienceNo abstract availabl

Immunization with HIV-1 gp41 Subunit Virosomes Induces Mucosal Antibodies Protecting Nonhuman Primates against Vaginal SHIV Challenges

SummaryHuman immunodeficiency virus (HIV)-1 is mainly transmitted mucosally during sexual intercourse. We therefore evaluated the protective efficacy of a vaccine active at mucosal sites. Macaca mulatta monkeys were immunized via both the intramuscular and intranasal routes with an HIV-1 vaccine made of gp41-subunit antigens grafted on virosomes, a safe delivery carrier approved in humans with self-adjuvant properties. Six months after 13 vaginal challenges with simian-HIV (SHIV)-SF162P3, four out of five vaccinated animals remained virus-negative, and the fifth was only transiently infected. None of the five animals seroconverted to p27gag-SIV. In contrast, all 6 placebo-vaccinated animals became infected and seroconverted. All protected animals showed gp41-specific vaginal IgAs with HIV-1 transcytosis-blocking properties and vaginal IgGs with neutralizing and/or antibody-dependent cellular-cytotoxicity activities. In contrast, plasma IgGs totally lacked virus-neutralizing activity. The protection observed challenges the paradigm whereby circulating antiviral antibodies are required for protection against HIV-1 infection and may serve in designing a human vaccine against HIV-1-AIDS