Alain Fischer

Summary

Country: France

Publications

  1. pmc Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
    J Clin Invest 118:3132-42. 2008
  2. ncbi request reprint [Gene therapy of children with X-linked severe combined immune deficiency: efficiency and complications]
    Alain Fischer
    INSERM U 429, Hopital Necker Enfants Malades, 149, rue de Sevres, 75015 Paris, France
    Med Sci (Paris) 20:115-7. 2004
  3. doi request reprint Shortening the immunodeficient period after hematopoietic stem cell transplantation
    Isabelle Andre-Schmutz
    INSERM, U768, Paris, 75015, France
    Immunol Res 44:54-60. 2009
  4. ncbi request reprint Human TCR alpha/beta+ CD4-CD8- double-negative T cells in patients with autoimmune lymphoproliferative syndrome express restricted Vbeta TCR diversity and are clonally related to CD8+ T cells
    Anne Bristeau-Leprince
    Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, Paris, France
    J Immunol 181:440-8. 2008
  5. ncbi request reprint Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes
    Véronique Mateo
    INSERM, U768, Paris, France
    Blood 110:4285-92. 2007
  6. ncbi request reprint Severe combined immunodeficiency. A model disease for molecular immunology and therapy
    Alain Fischer
    INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Immunol Rev 203:98-109. 2005
  7. pmc Integration of retroviruses: a fine balance between efficiency and danger
    Alain Fischer
    Department and the Inserm Research Unit 429 at Necker University Hospital, Paris, France
    PLoS Med 2:e10. 2005
  8. pmc The European rare diseases therapeutic initiative
    Alain Fischer
    Department of Pediatric Immunology, Necker University Hospital, Paris, France
    PLoS Med 2:e243. 2005
  9. ncbi request reprint CD3 deficiencies
    Alain Fischer
    Department of Pediatric Immuno Hematology and Inserm Unit 429, Necker Enfants Malades Hospital, Paris, France
    Curr Opin Allergy Clin Immunol 5:491-5. 2005
  10. ncbi request reprint Gene therapy for immunodeficiency diseases
    Alain Fischer
    INSERM U 429, Hopital Necker Enfants Malades, Paris, France
    Semin Hematol 41:272-8. 2004

Detail Information

Publications127 found, 100 shown here

  1. pmc Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
    J Clin Invest 118:3132-42. 2008
    ..Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer...
  2. ncbi request reprint [Gene therapy of children with X-linked severe combined immune deficiency: efficiency and complications]
    Alain Fischer
    INSERM U 429, Hopital Necker Enfants Malades, 149, rue de Sevres, 75015 Paris, France
    Med Sci (Paris) 20:115-7. 2004
  3. doi request reprint Shortening the immunodeficient period after hematopoietic stem cell transplantation
    Isabelle Andre-Schmutz
    INSERM, U768, Paris, 75015, France
    Immunol Res 44:54-60. 2009
    ..Here we summarize and discuss these results and their possible usage in the development of new cell therapies to shorten the immunodeficient period following hematopoietic stem cell transplantation...
  4. ncbi request reprint Human TCR alpha/beta+ CD4-CD8- double-negative T cells in patients with autoimmune lymphoproliferative syndrome express restricted Vbeta TCR diversity and are clonally related to CD8+ T cells
    Anne Bristeau-Leprince
    Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, Paris, France
    J Immunol 181:440-8. 2008
    ..CDR3 sequencing of matching clonotypes revealed a significant sharing of CDR3 sequences from selected Vbeta-Jbeta transcripts between DN and CD8+ T cells. Altogether, these data strongly argue for a CD8 origin of DN T cells in ALPS...
  5. ncbi request reprint Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes
    Véronique Mateo
    INSERM, U768, Paris, France
    Blood 110:4285-92. 2007
    ..Furthermore, they identified a novel AICD pathway as a unique alternative to Fas apoptosis in human peripheral T lymphocytes...
  6. ncbi request reprint Severe combined immunodeficiency. A model disease for molecular immunology and therapy
    Alain Fischer
    INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Immunol Rev 203:98-109. 2005
    ..SCID is thus a disease model for experimental therapy in the hematopoietic system...
  7. pmc Integration of retroviruses: a fine balance between efficiency and danger
    Alain Fischer
    Department and the Inserm Research Unit 429 at Necker University Hospital, Paris, France
    PLoS Med 2:e10. 2005
  8. pmc The European rare diseases therapeutic initiative
    Alain Fischer
    Department of Pediatric Immunology, Necker University Hospital, Paris, France
    PLoS Med 2:e243. 2005
  9. ncbi request reprint CD3 deficiencies
    Alain Fischer
    Department of Pediatric Immuno Hematology and Inserm Unit 429, Necker Enfants Malades Hospital, Paris, France
    Curr Opin Allergy Clin Immunol 5:491-5. 2005
    ..This review reports on the recent description of deleterious mutations in the genes encoding CD3 subunits expressed at the T-lymphocyte membrane in association with the T-cell receptor...
  10. ncbi request reprint Gene therapy for immunodeficiency diseases
    Alain Fischer
    INSERM U 429, Hopital Necker Enfants Malades, Paris, France
    Semin Hematol 41:272-8. 2004
    ..New advances in the technology of gene transfer should further promote gene therapy as a safe and effective therapeutic strategy of immunodeficiency diseases...
  11. ncbi request reprint [Gene therapy of severe combined immunodeficiency disease: proof of principle of efficiency and safety issues. Gene therapy, primary immunodeficiencies, retrovirus, lentivirus, genome]
    Alain Fischer
    INSERM U 429, Unité d Immunologie et Hématologie Pédiatrique et Département de Biothérapie, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris
    Bull Acad Natl Med 189:779-85; discussion 786-8. 2005
    ..Vector modifications, based mostly on inactivating the enhancer activity of the LTR, should preserve efficacy while improving safety...
  12. ncbi request reprint Genetic defects affecting lymphocyte cytotoxicity
    Alain Fischer
    Unité d Immunologie et Hématologie Pédiatrique, Assistance Publique, Hôpitaux de Paris Hôpital Necker Enfants Malades, 149 rue de Sevres, Paris
    Curr Opin Immunol 19:348-53. 2007
    ..Cytolytic cells exert a second effector function consisting of the secretion of cytokines, notably interferon gamma. The latter secretory process functions independently from the exocytic pathway of the lytic granules...
  13. doi request reprint Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells
    Fatine Benjelloun
    Institut National de la Santé et de la Recherche INSERM, U768, Universite Paris Descartes, Hopital Necker Enfants Malades, Paris, France
    Mol Ther 16:1490-9. 2008
    ..As a whole, our work provides a basis for supporting the gene therapy approach in Artemis-deficient SCID...
  14. pmc A primary immunodeficiency characterized by defective immunoglobulin class switch recombination and impaired DNA repair
    Sophie Peron
    Institut National de la Sante et de la Recherche Medicale, U768, Paris, France
    J Exp Med 204:1207-16. 2007
    ..Overall, these findings suggest that a unique Ig CSR deficiency phenotype could be related to an as-yet-uncharacterized defect in a DNA repair pathway involved in both CSR and SHM events...
  15. pmc Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal-Hreidarsson syndrome
    Fabien Touzot
    Institut National de la Sante et de la Recherche Medicale, U768, 75015 Paris, France
    Proc Natl Acad Sci U S A 107:10097-102. 2010
    ..These results identify Apollo as a crucial actor in telomere maintenance in vivo, independent of its function as a general DNA repair factor...
  16. ncbi request reprint Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly
    Dietke Buck
    INSERM, Hopital Necker Enfants Malades, U768 Unité Développement Normal et Pathologique du Système Immunitaire, Paris, France
    Cell 124:287-99. 2006
    ..All five patients carry mutations in the Cernunnos gene, which was identified through cDNA functional complementation cloning. Cernunnos/XLF represents a novel DNA repair factor essential for the NHEJ pathway...
  17. ncbi request reprint Inherited defects in lymphocyte cytotoxic activity
    Jana Pachlopnik Schmid
    Institut National de la Sante et de la Recherche Medicale INSERM, U768, 75015 Paris, France
    Immunol Rev 235:10-23. 2010
    ....
  18. doi request reprint Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients
    Chantal Lagresle-Peyrou
    Institut National de la Sante et de Recherche Medicale, Unit 768, Necker site, Paris, France
    Mol Ther 16:396-403. 2008
    ..This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation...
  19. pmc Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome")
    Jana Pachlopnik Schmid
    National Institute of Health and Medical Research INSERM Unit 768, Paris, France
    J Exp Med 209:2323-30. 2012
    ..Our results evidence the developmental impact of a Polε catalytic subunit deficiency in humans and its causal relationship with a newly recognized, inherited disorder...
  20. pmc Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey
    Marie Olivia Chandesris
    Hematology Department, Necker Enfants Malades Hospital, Assistance Publique Hopitaux de Paris, Paris, France
    Medicine (Baltimore) 91:e1-19. 2012
    ..Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented...
  21. pmc Temporal and spatial compartmentalization of drug-resistant cytomegalovirus (CMV) in a child with CMV meningoencephalitis: implications for sampling in molecular diagnosis
    Pierre Frange
    Unite d immunologie, Hématologie et Rhumatologie Pédiatrique, Assistance Publique Hopitaux de Paris AP HP, Hopital Necker Enfants Malades, Paris, France
    J Clin Microbiol 51:4266-9. 2013
    ..However, wild-type cytomegalovirus was evidenced in blood when the meningoencephalitis was diagnosed. Treatment of meningoencephalitis should be adapted to all previously identified resistance mutations in any compartment. ..
  22. ncbi request reprint Autoimmune lymphoproliferative syndrome with somatic Fas mutations
    Eliska Holzelova
    INSERM Unité 429, Hopital Necker Enfants Malades, Paris
    N Engl J Med 351:1409-18. 2004
    ..We studied six children with ALPS whose lymphocytes had normal sensitivity to Fas-induced apoptosis in vitro...
  23. ncbi request reprint Phosphorylation of Artemis following irradiation-induced DNA damage
    Catherine Poinsignon
    Développement Normal et Pathologique du Système Immunitaire INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Eur J Immunol 34:3146-55. 2004
    ..Thus, Artemis is an effector of DNA repair that can be phosphorylated by ATM, and possibly by DNA-PKcs and ATR depending upon the type of DNA damage...
  24. pmc Efficacy of gene therapy for X-linked severe combined immunodeficiency
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Necker Enfants Malades Hospital, Paris, France
    N Engl J Med 363:355-64. 2010
    ..We reviewed long-term outcomes after gene therapy in nine patients with X-linked severe combined immunodeficiency (SCID-X1), which is characterized by the absence of the cytokine receptor common gamma chain...
  25. doi request reprint Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability
    Tangui Le Guen
    Inserm U768, Paris, France
    Hum Mol Genet 22:3239-49. 2013
    ..Collectively, these results identify RTEL1 as a novel HHS-causing gene and highlight its role as a genomic caretaker in humans. ..
  26. ncbi request reprint Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients
    Nizar Mahlaoui
    Unité d Immunologie et Hématologie Pédiatrique, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    Pediatrics 120:e622-8. 2007
    ....
  27. doi request reprint Severe cutaneous bacillus Calmette-Guérin infection in immunocompromised children: the relevance of skin biopsy
    Amélie Gantzer
    Department of Dermatology, Hopital Necker Enfants Malades, Universite Rene Descartes, APHP, Paris, France
    J Cutan Pathol 40:30-7. 2013
    ..Skin biopsy is a useful part of the diagnostic workup for disseminated BCGitis, directing the clinician toward severe immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring immune restoration for prognostic purposes...
  28. doi request reprint [Chronic granulomatous disease: pathogenesis and therapy of associated fungal infections]
    ANNE DESJARDINS
    Service de Maladies Infectieuses et Tropicales, Hopital Necker Enfants Malades, Paris, France
    Med Sci (Paris) 28:963-9. 2012
    ..Here we review the genetic basis, pathogenesis and clinical presentation associated with fungal infections in chronic granulomatous disease as well as the current prophylaxis and newly available therapies...
  29. ncbi request reprint Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity
    Chantal Lagresle-Peyrou
    Universite Paris Descartes, Faculte de Medecine, INSERM Unit 429, Site Necker Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex15, France
    Blood 107:63-72. 2006
    ....
  30. ncbi request reprint Human leucocyte antigen-identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft-versus-host disease and pre-existing viral infe
    Raffaele Renella
    Unité d Immunologie et Hématologie Pédiatrique, Faculté de Médecine Université Réné Descartes, Paris, France
    Br J Haematol 134:510-6. 2006
    ..We suggest that the reduced survival after HLA-identical HSCT may be caused by the high incidence of pre-existing viral infections and associated with the onset of severe acute GVHD...
  31. doi request reprint FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function
    Aude Magerus-Chatinet
    Inserm U768, Paris, France
    Blood 113:3027-30. 2009
    ..Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS...
  32. pmc Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
    Sophie Peron
    Institut National de Santé et de Recherche Médicale, U768, 75015 Paris, France
    J Exp Med 205:2465-72. 2008
    ..It is characterized by the defective occurrence of double-strand DNA breaks (DSBs) in switch regions and abnormal formation of switch junctions. This observation strongly suggests a role for PMS2 in CSR-induced DSB generation...
  33. ncbi request reprint Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype
    Marina Cavazzana-Calvo
    Institut National de la Sante et de la Recherche Medicale, Unité 768, Paris, France
    Blood 109:4575-81. 2007
    ....
  34. doi request reprint Distinct severity of HLH in both human and murine mutants with complete loss of cytotoxic effector PRF1, RAB27A, and STX11
    Fernando E Sepulveda
    Inserm U768, Paris, France
    Blood 121:595-603. 2013
    ..Our data indicate that cytotoxic effectors may have other immune-regulatory roles in addition to their role in controlling viral replication...
  35. doi request reprint Blood CD4+CD45RO+CXCR5+ T cells are decreased but partially functional in signal transducer and activator of transcription 3 deficiency
    Fabienne Mazerolles
    Inserm U768, Paris, France University Sorbonne Paris Cité, and Pediatric Hematology and Immunology Unit, Necker Hospital, Paris, France
    J Allergy Clin Immunol 131:1146-56, 1156.e1-5. 2013
    ..Small numbers of nonactivated CD4+CD45RO+CXCR5+ T cells are also found in the blood...
  36. pmc Whole-exome sequencing identifies Coronin-1A deficiency in 3 siblings with immunodeficiency and EBV-associated B-cell lymphoproliferation
    Despina Moshous
    Inserm U768, Paris, France
    J Allergy Clin Immunol 131:1594-603. 2013
    ..We evaluated 3 siblings from a consanguineous family presenting with EBV-associated B-cell lymphoproliferation at an early age (12, 7½, and 14 months, respectively) and profound naive T-cell lymphopenia...
  37. pmc Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells
    Marjorie Côte
    Inserm U768, Hopital Necker Enfants Malades, Paris, France
    J Clin Invest 119:3765-73. 2009
    ..These data indicate that STXBP2 is required at a late step of the secretory pathway for the release of cytotoxic granules by binding syntaxin 11, another component of the intracellular membrane fusion machinery...
  38. doi request reprint Reduced immunoglobulin class switch recombination in the absence of Artemis
    Paola Rivera-Munoz
    Inserm U768, Paris, France
    Blood 114:3601-9. 2009
    ..Altogether, this indicates that Artemis participates in the repair of a subset of DNA breaks generated during CSR...
  39. ncbi request reprint Hematopoietic stem cell transplantation in Griscelli syndrome type 2: a single-center report on 10 patients
    Jana Pachlopnik Schmid
    INSERM, Unité U768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Paris, France
    Blood 114:211-8. 2009
    ..Additional studies are required to improve treatment...
  40. pmc Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1)
    Gael Menasche
    Unité de Recherhe sur le Développement Normal et Pathologique du Systéme Immunitaire, Hopital Necker Enfants Malades, Paris, France
    J Clin Invest 112:450-6. 2003
    ..This spectrum of GS conditions pinpoints the distinct molecular pathways used by melanocytes, neurons, and immune cells in secretory granule exocytosis, which in part remain to be unraveled...
  41. ncbi request reprint Successful allogeneic hemopoietic stem cell transplantation in a child who had anhidrotic ectodermal dysplasia with immunodeficiency
    Sophie Dupuis-Girod
    Unité d Immunologie et d Hématologie Pédiatriques, Institut National de la Santé et de la Recherche Médicale U429, Hopital Necker Enfants Malades, Paris, France
    Pediatrics 118:e205-11. 2006
    ..Hematopoietic stem cell transplantation is well tolerated and efficiently cures the profound immunodeficiency associated with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency...
  42. pmc A human postnatal lymphoid progenitor capable of circulating and seeding the thymus
    Emmanuelle M Six
    Institut National de la Sante et de la Recherche Medicale INSERM, U768, 75015 Paris, France
    J Exp Med 204:3085-93. 2007
    ..Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus...
  43. doi request reprint Haematopoietic stem cell transplantation for SCID patients: where do we stand?
    Marina Cavazzana-Calvo
    Département de Biothérapie, AP HP, Hôpital Universitaire Necker Enfants Malades, Paris, France
    Br J Haematol 160:146-52. 2013
    ..New approaches for reconstituting T cell compartments more rapidly are under intense preclinical development and are discussed herein...
  44. doi request reprint Heterogeneous telomere defects in patients with severe forms of dyskeratosis congenita
    Fabien Touzot
    INSERM, U768, Paris, France
    J Allergy Clin Immunol 129:473-82, 482.e1-3. 2012
    ..Hoyeraal-Hreidarsson syndrome (HH) is a severe variant of DC in which an early onset of bone marrow failure leading to combined immunodeficiency is associated with microcephaly, cerebellar hypoplasia, and growth retardation...
  45. pmc The C-terminal domain of Cernunnos/XLF is dispensable for DNA repair in vivo
    Laurent Malivert
    Inserm U768, Malades, U768, Unité de Développement Normal et Pathologique du Système Immunitaire, Hopital Necker Enfants Malades, 149, rue de Sevres, 75015 Paris, France
    Mol Cell Biol 29:1116-22. 2009
    ..We demonstrate here, using in vitro-generated Cernunnos mutants and a series of functional assays in vivo, that the C-terminal region of Cernunnos is dispensable for its activity during DNA repair...
  46. ncbi request reprint Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV
    Dietke Buck
    INSERM, Hopital Necker Enfants Malades, U429, Unité Développement Normal et Pathologique du Système Immunitaire, Paris, France
    Eur J Immunol 36:224-35. 2006
    ..These observations contrast with the severity of the clinical immunodeficiency, suggesting that Lig4 may have additional critical roles in lymphocyte survival beyond V(D)J recombination...
  47. ncbi request reprint Gene therapy for severe combined immunodeficiency
    Marina Cavazzana-Calvo
    Département de Biothérapie, Hopital Necker Enfants Malades, 75015 Paris, France
    Annu Rev Med 56:585-602. 2005
    ..This review discusses recent developments in SCID identification and treatment...
  48. pmc Regulation of natural cytotoxicity by the adaptor SAP and the Src-related kinase Fyn
    Coralie Bloch-Queyrat
    Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Unité Institut National de la Santé et de la Recherche Medicale 429, Hopital Necker Enfants Malades, 75015 Paris, France
    J Exp Med 202:181-92. 2005
    ..They also could help to explain the high propensity of patients who have XLP disease to develop lymphoproliferative disorders...
  49. doi request reprint Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype
    Romain Micol
    CEREDIH, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris, 75743 Paris Cedex 15, France
    J Allergy Clin Immunol 128:382-9.e1. 2011
    ..The course of the disease is characterized by neurologic manifestations, infections, and cancers...
  50. pmc Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I
    Anne Puel
    Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sante et de la Recherche Medicale INSERM, U550, 75015 Paris, France
    J Exp Med 207:291-7. 2010
    ..These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I...
  51. ncbi request reprint IL-7 effect on immunological reconstitution after HSCT depends on MHC incompatibility
    Isabelle Andre-Schmutz
    INSERM U 429, Hopital Necker Enfants Malades, Paris, France
    Br J Haematol 126:844-51. 2004
    ....
  52. ncbi request reprint Artemis sheds new light on V(D)J recombination
    Francoise Le Deist
    Developpement Normal et Pathologique du Systeme Immunitaire, INSERM U429, Paris, France
    Immunol Rev 200:142-55. 2004
    ..New conditions of immune deficiency in humans are now under investigations and should lead to the identification of additional V(D)J recombination/DNA repair factors...
  53. ncbi request reprint Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis
    Gael Menasche
    INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Immunol Rev 203:165-79. 2005
    ..This review focuses on several effectors of this secretory pathway, recently identified, because their defects cause these disorders, and discusses their role and molecular interactions in granule-dependent cytotoxic activity...
  54. ncbi request reprint Severe and progressive encephalitis as a presenting manifestation of a novel missense perforin mutation and impaired cytolytic activity
    Jerome Feldmann
    Inistitut National de la Santé et de la Recherche Médicale INSERM U429, Hopital Necker Enfants Malades, 149 rue de Sevres, 75743 Paris, Cedex 15, France
    Blood 105:2658-63. 2005
    ..This observation also raises the question of the role of some mutations in the neurologic expression of FHL...
  55. ncbi request reprint The block in immunoglobulin class switch recombination caused by activation-induced cytidine deaminase deficiency occurs prior to the generation of DNA double strand breaks in switch mu region
    Nadia Catalan
    Institut National de la Sante et de la Recherche Medicale, Unite 429, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    J Immunol 171:2504-9. 2003
    ....
  56. pmc Human iNKT and MAIT cells exhibit a PLZF-dependent proapoptotic propensity that is counterbalanced by XIAP
    Stéphane Gerart
    Unité Inserm 768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Hopital Necker Enfants Malades, Paris, France
    Blood 121:614-23. 2013
    ..The proapoptotic feature of iNKT cells also gives a reliable explanation of their exhaustion observed in different human conditions including the XIAP immunodeficiency...
  57. doi request reprint Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients
    Monia Ouederni
    Pediatric Hematology Immunology Unit, Assistance Publique Hopitaux de Paris, Necker Hospital, France
    Blood 118:5108-18. 2011
    ..RFXANK deficiency is a severe, often fatal CID for which HSCT is the only curative treatment. However, some patients may survive for relatively long periods if multiple prophylactic measures are implemented...
  58. doi request reprint Human MSH6 deficiency is associated with impaired antibody maturation
    Pauline Gardès
    Inserm U768, Hopital Necker Enfants Malades, F 75015 Paris, France
    J Immunol 188:2023-9. 2012
    ..These data suggest that in human CSR, MSH6 is involved in both the induction and repair of DNA double-strand breaks in switch regions...
  59. ncbi request reprint Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency
    Frederic Rieux-Laucat
    INSERM Unité 768, Hopital Necker, Paris, France
    N Engl J Med 354:1913-21. 2006
    ....
  60. doi request reprint A histidine in the beta-CASP domain of Artemis is critical for its full in vitro and in vivo functions
    Jean Pierre de Villartay
    Inserm U768, Unité Développement Normal et Pathologique du Système Immunitaire, Hopital Necker Enfants Malades, 149 rue de Sevres, Paris F 75015, France
    DNA Repair (Amst) 8:202-8. 2009
    ..Moreover, inherited mutation of H254 results in radiosensitive severe combined immune deficiency (RS-SCID) in humans. This residue might play a key role in specificity towards DNA, if not directly in zinc binding...
  61. ncbi request reprint Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients
    Marie Ouachée-Chardin
    Department of Pediatric Immuno Hematology, Necker Enfants Malades Hospital, Paris, France
    Pediatrics 117:e743-50. 2006
    ..Chemotherapy- or immunotherapy-based treatments can achieve remission. Hematopoietic stem cell transplantation (HSCT), however, is the only curative option, but optimal modalities and long-term outcome are not yet well known...
  62. doi request reprint Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency)
    Jana Pachlopnik Schmid
    INSERM Unité 768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Hopital Necker Enfants Malades, Paris, France
    Blood 117:1522-9. 2011
    ..This first phenotypic comparison of XLP subtypes should help to improve the diagnosis and the care of patients with XLP conditions...
  63. doi request reprint Reduced expression of FOXP3 and regulatory T-cell function in severe forms of early-onset autoimmune enteropathy
    Nicolette Moes
    Universite Paris Descartes, Paris, France
    Gastroenterology 139:770-8. 2010
    ..We analyzed the molecular basis of neonatal or early postnatal AIE using clinical, genetic, and functional immunological studies...
  64. ncbi request reprint Analysis of class switch recombination and somatic hypermutation in patients affected with autosomal dominant hyper-IgM syndrome type 2
    Kohsuke Imai
    Institut National de la Santé et de la Recherche Médicale INSERM Unité 429, Hopital Necker Enfants Malades, Paris, France
    Clin Immunol 115:277-85. 2005
    ..The characteristics of the AD-HIGM2 phenotype indicate that the AID C-terminal region may be involved in DNA repair machinery required for CSR...
  65. ncbi request reprint Efficacy of gene therapy for SCID is being confirmed
    Marina Cavazzana-Calvo
    Département de Biothérapie, Hopital Necker Enfants Malades, 75015 Paris, France
    Lancet 364:2155-6. 2004
  66. doi request reprint Hypomorphic mutation of ZAP70 in human results in a late onset immunodeficiency and no autoimmunity
    Capucine Picard
    Centre d Etude des Déficits Immunitaires, Assistance Publique Hopitaux de Paris, Hopital Necker Enfants Malades, EU, Paris, France
    Eur J Immunol 39:1966-76. 2009
    ..This report extends the phenotype spectrum of ZAP70 deficiency with a residual function of ZAP70...
  67. pmc Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3
    Genevieve De Saint Basile
    Unité Développement Normal et Pathologique du Système Immunitaire, INSERM U 429, Paris, France
    J Clin Invest 114:1512-7. 2004
    ..e., CD3epsilon deficiency, and emphasize the essential roles played by the CD3epsilon and CD3delta subunits in human thymocyte development, since these subunits associate with both the pre-TCR and the TCR...
  68. ncbi request reprint [Defect in lytic granule exocytosis: several causes, a same effect]
    Gael Menasche
    Inserm U768, Hopital Necker Enfants Malades, 149, rue de Sevres, 75015 Paris, France
    Med Sci (Paris) 22:733-8. 2006
    ..Future investigations regarding HS will continue to elucidate this exocytic pathway machinery and improve our understanding of how it finely regulates the immune response, an area that is likely to be useful for therapeutic intervention...
  69. pmc Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex
    Mathieu Kurowska
    INSERM Unité U768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Paris, France
    Blood 119:3879-89. 2012
    ..Our data provide further molecular insights into the key functional and regulatory mechanisms underlying the terminal transport of cytotoxic granules and the latter's secretion at the immune synapse...
  70. doi request reprint Strategies for retrovirus-based correction of severe, combined immunodeficiency (SCID)
    Alain Fischer
    Descartes University of Paris, Paris, France
    Methods Enzymol 507:15-27. 2012
    ..Design of vectors in which the enhancer element of retroviral LTR has been deleted and an internal promoter added (self-inactivated vectors) could provide both safe and efficient gene transfer as being presently tested...
  71. doi request reprint Invasive mold infections in chronic granulomatous disease: a 25-year retrospective survey
    Sophie Blumental
    Immunology and Haematology Unit, Hopital Necker Enfants Malades, Paris, France
    Clin Infect Dis 53:e159-69. 2011
    ..This study offers a descriptive review of invasive mold infection (mIFI) in children with CGD over an extended period of time...
  72. ncbi request reprint Activation-induced cytidine deaminase: structure-function relationship as based on the study of mutants
    Anne Durandy
    Institut National de la Sante et de la Recherche Medicale INSERM, U768, Hopital Necker Enfants Malades, Paris, France
    Hum Mutat 27:1185-91. 2006
    ....
  73. doi request reprint Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency
    Benedicte Neven
    Unité d Immuno Hématologie et Rhumatologie Pédiatrique, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris, Paris, France
    Blood 113:4114-24. 2009
    ..In most cases, HSCT enables long-term survival with infrequent sequelae. However, the occurrence of relatively late-onset complications is a concern that requires specific means of prevention and justifies careful patient follow-up...
  74. ncbi request reprint Immune reconstitution after haematopoietic stem cell transplantation: obstacles and anticipated progress
    Marina Cavazzana-Calvo
    Assistance Publique Hopitaux de Paris AP HP, Department of Biotherapy, Hopital Necker Enfants Malades, Paris, France
    Curr Opin Immunol 21:544-8. 2009
    ..If these objectives could be achieved, the haploidentical procedure would become more readily available to patients affected by acquired or inherited disorders of the haematopoietic system...
  75. ncbi request reprint A newly identified isoform of Slp2a associates with Rab27a in cytotoxic T cells and participates to cytotoxic granule secretion
    Gael Menasche
    Laboratoire du Développement Normal et Pathologique du Système Immunitaire, INSERM, Unité U768, Paris, France
    Blood 112:5052-62. 2008
    ..The overexpression of a dominant-negative form of Slp2a-hem markedly impaired exocytosis of cytotoxic granules-indicating that Slp2a is required for cytotoxic granule docking at the immunologic synapse...
  76. pmc STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity
    Capucine Picard
    Assistance Publique Hopitaux de Paris, Hopital Necker Enfants Malades, Paris
    N Engl J Med 360:1971-80. 2009
    ..Two of these patients have a homozygous nonsense mutation in STIM1 that abrogates expression of STIM1 and Ca(2+) influx...
  77. ncbi request reprint Hyper-immunoglobulin M syndromes caused by intrinsic B-lymphocyte defects
    Anne Durandy
    INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Immunol Rev 203:67-79. 2005
    ..The mechanism of action of AID remains somewhat debated, but the observation that uracil-DNA-glycosylase deficiency leads to a severe hyper-IgM syndrome strongly argues in favor of a DNA-editing activity of AID...
  78. ncbi request reprint Allogeneic bone marrow transplantation in mevalonic aciduria
    Benedicte Neven
    Unité d Immuno Hématologie et Rhumatologie Pédiatrique, Assistance Publique Hopitaux de Paris, Paris, France
    N Engl J Med 356:2700-3. 2007
    ..We observed sustained remission of febrile attacks and inflammation during a 15-month follow-up period...
  79. pmc Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness
    Chantal Lagresle-Peyrou
    Research Laboratory on Normal and Pathologic Development of the Immune System, U768, Institut National de la Sante et de la Recherche Medicale, 75015 Paris, France
    Nat Genet 41:106-11. 2009
    ..These results identify a previously unknown mechanism involved in regulation of hematopoietic cell differentiation and in one of the most severe human immunodeficiency syndromes...
  80. ncbi request reprint Hyper-immunoglobulin-M syndromes caused by an intrinsic B cell defect
    Anne Durandy
    INSERM U429, Hospital Necker Sick Children, Paris, France
    Curr Opin Allergy Clin Immunol 3:421-5. 2003
    ....
  81. ncbi request reprint Gene therapy of RAG-2-/- mice: sustained correction of the immunodeficiency
    Frank Yates
    Institut National de la Santé et de la Recherche Médicale INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Blood 100:3942-9. 2002
    ..Altogether, this study demonstrates the efficiency of ex vivo RAG-2 gene transfer in HSCs to correct the immune deficiency of RAG-2-/- mice, constituting a significant step toward clinical application...
  82. ncbi request reprint Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy
    Salima Hacein-Bey-Abina
    Laboratoire INSERM, Hopital Necker Enfants Malades, Paris, France
    N Engl J Med 346:1185-93. 2002
    ..We investigated whether infusion of autologous hematopoietic stem cells that had been transduced in vitro with the gamma(c) gene can restore the immune system in patients with severe combined immunodeficiency...
  83. ncbi request reprint Gene therapy of X-linked severe combined immunodeficiency
    Marina Cavazzana-Calvo
    INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Curr Opin Allergy Clin Immunol 2:507-9. 2002
    ..Definitive conclusions cannot be thrown due to the limited number of gene therapy-treated patients and their relatively short follow-up...
  84. pmc Gene therapy for severe combined immunodeficiency: are we there yet?
    Marina Cavazzana-Calvo
    INSERM U768 and Université Paris Descartes, Paris, France
    J Clin Invest 117:1456-65. 2007
    ..In this review, we summarize the advantages and limitations associated with the use of gene therapy to cure SCID. Insertional mutagenesis and technological improvements aimed at increasing the safety of this strategy are also discussed...
  85. doi request reprint Gene therapy of inherited diseases
    Alain Fischer
    INSERM Unit 768, Paris, France alain fi
    Lancet 371:2044-7. 2008
  86. ncbi request reprint Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome
    Marc Tardieu
    Service de Neurologie, Département de Pédiatrie et Laboratoire de Neuropathologie, Hopital Bicetre, Assistance Publique Hopitaux de Paris, Paris, France
    Blood 106:40-2. 2005
    ..We also reviewed the very long-term outcome of the other 11 patients with Chediak-Higashi syndrome who had received bone marrow transplants at our center since 1981. All displayed neurologic deficits or low cognitive abilities...
  87. ncbi request reprint Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study
    Sylvain Choquet
    Hematology Unit, CHU La Pitié Salpêtrière Hospital, 47 bd de l Hopital, 75651 Paris Cedex 14, France
    Blood 107:3053-7. 2006
    ..We conclude that rituximab is effective and safe in PTLD, with stable responses at 1 year. The response rate and overall survival might be improved by combining rituximab with other treatments...
  88. ncbi request reprint [Severe combined immunodeficiency: susceptibility to HPV?]
    Francoise Le Deist
    Centre d Etude des Déficits Immunitaires, Hopital Necker Enfants Malades, 149, rue de Sevres, 75015 Paris, France
    Med Sci (Paris) 21:125-7. 2005
  89. ncbi request reprint Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group
    Jean Donadieu
    Service d hémato oncologie pédiatrique, Hopital Trousseau, Paris, France
    Haematologica 90:45-53. 2005
    ..Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced the frequency and severity of infections, but its possible influence on the risk of malignancy is not known...
  90. ncbi request reprint Hematopoietic stem cell transplantation and other management strategies for MHC class II deficiency
    Capucine Picard
    Study Center of Primary Immunodeficiencies, Necker Hospital, Assistance Publique Hopitaux de Paris, 149 rue de Sevres, Paris 75015, France
    Immunol Allergy Clin North Am 30:173-8. 2010
    ..Hematopoietic stem cell transplantation is the only known treatment available to cure MHC class II expression deficiency...
  91. ncbi request reprint Gene therapy of X-linked severe combined immunodeficiency
    Salima Hacein-Bey-Abina
    INSERM U 429, Gene and Cell Therapy Unit, Hĵpital Necker Enfants Malades, Paris, France
    Int J Hematol 76:295-8. 2002
    ..These 8 patients are doing well and living in a normal environment. This yet successful gene therapy demonstrates that in a setting where transgene expression provides a selective advantage, a clinical benefit can be expected...
  92. ncbi request reprint Gene therapy of severe combined immunodeficiencies
    Alain Fischer
    INSERM U429, Hopital Necker, 149 rue de Sevres, 75015 Paris, France
    Nat Rev Immunol 2:615-21. 2002
    ..Nevertheless, severe combined immunodeficiencies are a useful model, because gene transfer can confer a selective advantage to transduced cells. In this way, a proof of concept for gene therapy has been provided...
  93. pmc Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis
    Despina Moshous
    Unité Développement Normal et Pathologique du Système Immunitaire, Institut National de la Santé et de la Recherche Médicale INSERM U429, Hopital Necker Enfants Malades, Paris, France
    J Clin Invest 111:381-7. 2003
    ..This syndrome emphasizes the role of Artemis in the NHEJ pathway of DNA repair and suggests that other, yet ill-defined, conditions associating immunodeficiency and lymphoma could be caused by mutations in genes encoding NHEJ factors...
  94. ncbi request reprint Gene therapy for primary immunodeficiencies
    Alain Fischer
    Developpement Normal et Pathologique du Systeme Immunitaire, INSERM U 768, Hopital Necker, 149 rue de Sevres, Paris 75015, France
    Immunol Allergy Clin North Am 30:237-48. 2010
    ..There is now a strong rationale in support of gene therapy for at least some PIDs, as discussed in this article...
  95. ncbi request reprint Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gammac cytokine receptor subunit or JAK-3 deficiency
    Caroline Laffort
    Unite d immunologie, d Hématologie, et de Rhumatologie Pédiatrique, Paris, France
    Lancet 363:2051-4. 2004
    ..That genetic causes are the only predisposing factor to be identified for severe combined immune deficiency, suggests that natural-killer cells or gammac/JAK-3-dependent signalling in keratinocytes could have a role in anti-HPV immunity...
  96. ncbi request reprint Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99
    Corinne Antoine
    Service de Biostatistique et Service d Immunologie et d Hématologie Pédiatrique, Hopital Necker Enfants Malades, Paris, France
    Lancet 361:553-60. 2003
    ..This European report focuses on the long-term results of such procedures done between 1968 and December, 1999, for primary immunodeficiencies...
  97. ncbi request reprint Defective cytotoxic granule-mediated cell death pathway impairs T lymphocyte homeostasis
    Genevieve De Saint Basile
    Hopital Necker, Paris, France
    Curr Opin Rheumatol 15:436-45. 2003
    ..These disorders highlight the determinant role of this lytic pathway in the control of lymphocyte expansion and homeostasis. New effectors of this secretory pathway have been thus identified...
  98. ncbi request reprint Functional consequences of perforin gene mutations in 22 patients with familial haemophagocytic lymphohistiocytosis
    Jerome Feldmann
    Unité de Recherche sur le Développement Normal et Pathologique du Système Immunitaire, INSERM U429, Hopital Necker Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France
    Br J Haematol 117:965-72. 2002
    ..Altogether, these data enabled a better characterization of perforin deficiency and its consequences, and defined reliable diagnostic tools...
  99. ncbi request reprint Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules
    Genevieve De Saint Basile
    Institut National de la Sante et de la Recherche Medicale INSERM, U768, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    Nat Rev Immunol 10:568-79. 2010
    ..We explore the possibility that comparison of these two kinetically and spatially regulated secretory pathways will provide clues to uncover additional effectors that regulate the cytotoxic function of lymphocytes...
  100. ncbi request reprint Adenovirally transduced dendritic cells induce bispecific cytotoxic T lymphocyte responses against adenovirus and cytomegalovirus pp65 or against adenovirus and Epstein-Barr virus EBNA3C protein: a novel approach for immunotherapy
    Yamina Hamel
    INSERM U429, Hopital Necker Enfants Malades, 75743 Paris Cedex 15, France
    Hum Gene Ther 13:855-66. 2002
    ..Therefore, this approach could be considered in order to generate efficient virus cytolytic T cells to be used as adoptive immunotherapy in transplanted patients...
  101. ncbi request reprint Gene therapy of metabolic diseases
    Alain Fischer
    INSERM, U768, Paris, France
    J Inherit Metab Dis 29:409-12. 2006
    ..A significant safety issue has also been observed. Several strategies are being experimentally tested for a number of metabolic diseases (more than 20) and may provide a rationale for the future development of clinical trials...