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Christine Hanssen Rinaldo - One of the best experts on this subject based on the ideXlab platform.

  • treatment of progressive multifocal leukoencephalopathy with Interleukin 7
    JAMA Neurology, 2014
    Co-Authors: Therese Croughs, Stian Henriksen, Christine Hanssen Rinaldo, Céline Leboeuf, Irini Sereti, Karl Bjornar Alstadhaug, Hans H Hirsch
    Abstract:

    Importance No reliable treatment options are known for progressive multifocal leukoencephalopathy with underlying immunodeficiency. We describe successful compassionate use of recombinant human Interleukin 7 in a patient with idiopathic CD4 + T-cell lymphocytopenia. Observations After the diagnoses of progressive multifocal leukoencephalopathy and idiopathic CD4 + T-cell lymphocytopenia were established, a 61-year-old man was treated with recombinant human Interleukin 7 on November 1, 2012. Except for an episode of epilepsia partialis continua on January 16, 2013, a gradual clinical improvement was observed until March. Abnormalities shown on magnetic resonance imaging regressed; JC virus DNA in plasma, likely originating from the brain based on sequencing data, cleared; and increases in peripheral CD4 + T cells and JC virus intrathecal antibodies were observed. One year after treatment, the CD4 + T-cell count returned to baseline and the clinical improvement waned, possibly due to the patient’s complex epilepsy. On the latest evaluation on January 14, 2014, the patient’s condition was unchanged, with no signs of ongoing central nervous system infection. Conclusions and Relevance The present case argues strongly for proof of the treatment concept. However, deeper insight into the JC virus and its pathogenesis and the immune response during central nervous system infection as well as further clinical studies are needed before recombinant human Interleukin 7 can be recommended for the treatment of other cases of immunodeficiency and progressive multifocal leukoencephalopathy.

Karl Bjornar Alstadhaug - One of the best experts on this subject based on the ideXlab platform.

  • treatment of progressive multifocal leukoencephalopathy with Interleukin 7
    JAMA Neurology, 2014
    Co-Authors: Therese Croughs, Stian Henriksen, Christine Hanssen Rinaldo, Céline Leboeuf, Irini Sereti, Karl Bjornar Alstadhaug, Hans H Hirsch
    Abstract:

    Importance No reliable treatment options are known for progressive multifocal leukoencephalopathy with underlying immunodeficiency. We describe successful compassionate use of recombinant human Interleukin 7 in a patient with idiopathic CD4 + T-cell lymphocytopenia. Observations After the diagnoses of progressive multifocal leukoencephalopathy and idiopathic CD4 + T-cell lymphocytopenia were established, a 61-year-old man was treated with recombinant human Interleukin 7 on November 1, 2012. Except for an episode of epilepsia partialis continua on January 16, 2013, a gradual clinical improvement was observed until March. Abnormalities shown on magnetic resonance imaging regressed; JC virus DNA in plasma, likely originating from the brain based on sequencing data, cleared; and increases in peripheral CD4 + T cells and JC virus intrathecal antibodies were observed. One year after treatment, the CD4 + T-cell count returned to baseline and the clinical improvement waned, possibly due to the patient’s complex epilepsy. On the latest evaluation on January 14, 2014, the patient’s condition was unchanged, with no signs of ongoing central nervous system infection. Conclusions and Relevance The present case argues strongly for proof of the treatment concept. However, deeper insight into the JC virus and its pathogenesis and the immune response during central nervous system infection as well as further clinical studies are needed before recombinant human Interleukin 7 can be recommended for the treatment of other cases of immunodeficiency and progressive multifocal leukoencephalopathy.

  • Treatment of ProgressiveMultifocal Leukoencephalopathy With Interleukin 7
    2014
    Co-Authors: Karl Bjornar Alstadhaug, Stian Henriksen, Irini Sereti
    Abstract:

    P rogressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the brain caused by JC virus (JCV) replication in oligodendrocytes. The disease affects immunocompromised individuals and is usually fatal within months.1 Delgado-Alvarado et al2 described 1 patient with PML and idiopathic CD4+ T-cell lymphocytopenia (ICL) and reviewed 12 previous cases. Idiopathic CD4+ T-cell lymphocytopenia is diagnosedwhen absolute CD4+ T-cell counts are less than 300/μL on 2 ormore occasions in the absence of potential causes of immunodeficiency, including immunosuppressive therapies and infections with human immunodeficiency virus (HIV) and human T-lymphotropic virus.3We diagnosed ICL and PML in a patient and treated him with recombinant human Interleukin 7 (rhIL-7).

Klaus Müller - One of the best experts on this subject based on the ideXlab platform.

Scott K. Durum - One of the best experts on this subject based on the ideXlab platform.

  • The major isoforms of Bim contribute to distinct biological activities that govern the processes of autophagy and apoptosis in Interleukin-7 dependent lymphocytes.
    Biochimica et biophysica acta, 2012
    Co-Authors: Shannon M. Ruppert, Scott K. Durum, Ge Zhang, Adina L. Carlson, Arati Limaye, Annette R. Khaled
    Abstract:

    Bim is a BH3-only member of the Bcl-2 family that enables the death of T-cells. Partial rescue of cytokine-deprived T-cells occurs when Bim and the receptor for the T-cell growth factor, Interleukin-7, are deleted, implicating Bim as a possible target of Interleukin-7-mediated signaling. Alternative splicing yields three major isoforms: BimEL, BimL and BimS. To study the effect of Bim deficiency and define the function of the major isoforms, Bim-containing and Bim-deficient T-cells, dependent on Interleukin-7 for growth, were used. Loss of total Bim in Interleukin-7-deprived T-cells resulted in delayed apoptosis. However, loss of Bim also impeded the later degradative phase of autophagy. p62, an autophagy-adaptor protein which is normally degraded, accumulated in Bim deficient cells. To explain this, BimL was found to support acidification of lysosomes that later may associate with autophagic vesicles. Key findings showed that inhibition of lysosomal acidification accelerated death upon Interleukin-7 withdrawal only in Bim-containing T-cells. intereukin-7 dependent T-cells lacking Bim were less sensitive to inhibition of lysosomal acidification. BimL co-immunoprecipitated with dynein and Lamp1-containing vesicles, indicating BimL could be an adaptor for dynein to facilitate loading of lysosomes. In Bim deficient T-cells, lysosome-tracking probes revealed vesicles of less acidic pH. Over-expression of BimL restored acidic vesicles in Bim deficient T-cells, while other isoforms, BimEL and BimS, promoted intrinsic cell death. These results reveal a novel role for BimL in lysosomal positioning that may be required for the formation of degradative autolysosomes.

  • Interleukin-7 receptor expression: intelligent design
    Nature reviews. Immunology, 2007
    Co-Authors: Renata Mazzucchelli, Scott K. Durum
    Abstract:

    Interleukin-7 (IL-7) is produced by stromal cells in lymphoid tissues and is required for the development of T cells and for their persistence in the periphery. Unlike many other cytokines that act on lymphocytes, IL-7 production by stromal cells is not substantially affected by extrinsic stimuli. So, the amount of available IL-7 protein is thought to be regulated by the rate that it is scavenged by T cells. As we review here, there is mounting evidence indicating that the amount of IL-7 receptor expressed on a cell not only determines how vigorously the cell responds to IL-7, but it can also determine how efficiently the cell consumes IL-7 and, therefore, affect the supply of this limiting resource in the niche.

  • Interleukin-7: physiological roles and mechanisms of action
    Cytokine & growth factor reviews, 1999
    Co-Authors: R. Hofmeister, Annette R. Khaled, N. Benbernou, Éva Rajnavölgyi, Kathrin Muegge, Scott K. Durum
    Abstract:

    Interleukin-7 (IL-7), a product of stromal cells, provides critical signals to lymphoid cells at early stages in their development. Two types of cellular responses to IL-7 have been identified in lymphoid progenitors: (1) a trophic effect and (2) an effect supporting V(D)J recombination. The IL-7 receptor is comprised of two chains, IL-7R alpha and gamma(c). Following receptor crosslinking, rapid activation of several classes of kinases occurs, including members of the Janus and Src families and PI3-kinase. A number of transcription factors are subsequently activated including STATs, c-myc, NFAT and AP-1. However, it remains to be determined which, if any, previously identified pathway leads to the trophic or V(D)J endpoints. The trophic response to IL-7 involves protecting lymphoid progenitors from a death process that resembles apoptosis. This protection is partly mediated by IL-7 induction of Bcl-2, however other IL-7-induced events are probably also involved in the trophic response. The V(D)J response to IL-7 is partly mediated through increased production of Rag proteins (which cleave the target locus) and partly by increasing the accessibility of a target locus to cleavage through chromatin remodeling.

Therese Croughs - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy of recombinant human Interleukin 7 in a patient with severe lymphopenia-related progressive multifocal leukoencephalopathy.
    Open forum infectious diseases, 2014
    Co-Authors: Jacques Gasnault, Therese Croughs, Marie-ghislaine De Goër De Herve, Jean-marie Michot, Houria Hendel-chavez, Vannina Seta, Anne-aurélie Mazet, Bruno Stankoff, Jean-henri Bourhis, Olivier Lambotte
    Abstract:

    In this study, we report the case of a patient with profound lymphopenia after allogenic bone marrow transplantation who developed severe progressive multifocal leukoencephalopathy. Single-agent recombinant human Interleukin-7 therapy was associated with restoration of anti-John Cunningham polyomavirus (JCV) T-cell responses, JCV clearance from cerebrospinal fluid, and a dramatic clinical improvement.

  • treatment of progressive multifocal leukoencephalopathy with Interleukin 7
    JAMA Neurology, 2014
    Co-Authors: Therese Croughs, Stian Henriksen, Christine Hanssen Rinaldo, Céline Leboeuf, Irini Sereti, Karl Bjornar Alstadhaug, Hans H Hirsch
    Abstract:

    Importance No reliable treatment options are known for progressive multifocal leukoencephalopathy with underlying immunodeficiency. We describe successful compassionate use of recombinant human Interleukin 7 in a patient with idiopathic CD4 + T-cell lymphocytopenia. Observations After the diagnoses of progressive multifocal leukoencephalopathy and idiopathic CD4 + T-cell lymphocytopenia were established, a 61-year-old man was treated with recombinant human Interleukin 7 on November 1, 2012. Except for an episode of epilepsia partialis continua on January 16, 2013, a gradual clinical improvement was observed until March. Abnormalities shown on magnetic resonance imaging regressed; JC virus DNA in plasma, likely originating from the brain based on sequencing data, cleared; and increases in peripheral CD4 + T cells and JC virus intrathecal antibodies were observed. One year after treatment, the CD4 + T-cell count returned to baseline and the clinical improvement waned, possibly due to the patient’s complex epilepsy. On the latest evaluation on January 14, 2014, the patient’s condition was unchanged, with no signs of ongoing central nervous system infection. Conclusions and Relevance The present case argues strongly for proof of the treatment concept. However, deeper insight into the JC virus and its pathogenesis and the immune response during central nervous system infection as well as further clinical studies are needed before recombinant human Interleukin 7 can be recommended for the treatment of other cases of immunodeficiency and progressive multifocal leukoencephalopathy.