Genomes and Genes
- Highly restricted human T cell repertoire in peripheral blood and tissue-infiltrating lymphocytes in Omenn's syndromeF Rieux-Laucat
Unité INSERM 429, Hopital Necker Enfants Malades, 75743 Paris, Cedex 15, France
J Clin Invest 102:312-21. 1998..These results suggest that the oligoclonal expansion of T cells observed in Omenn's syndrome could be the consequence of autoimmune proliferation generated by a profound defect in lymphocyte development...
- Inherited and somatic CD3zeta mutations in a patient with T-cell deficiencyFrederic Rieux-Laucat
INSERM Unité 768, Hopital Necker, Paris, France
N Engl J Med 354:1913-21. 2006....
- Inherited and acquired death receptor defects in human Autoimmune Lymphoproliferative SyndromeFrederic Rieux-Laucat
Unité INSERM 429, Universite Paris V, Hopital Necker Enfants Malades, Paris, France
Curr Dir Autoimmun 9:18-36. 2006..Consequences of this finding will be discussed in terms of functional and molecular diagnosis as well as in the understanding of the pathophysiological basis of ALPS...
- [Autoimmune lymphoproliferative syndrome: an inherited or a somatic defect of apoptosis]Frederic Rieux-Laucat
Inserm U768, Universite Paris V, Hopital Necker, 149, rue de Sevres, 75015 Paris, France
Med Sci (Paris) 22:645-50. 2006..These findings might have important implications in deciphering the pathophysiological bases of other autoimmune diseases...
- Cell-death signaling and human diseaseFrederic Rieux-Laucat
Institut National de la Santé et de la Recherche Médicale U429, Hopital Necker Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France
Curr Opin Immunol 15:325-31. 2003....
- Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathwaysF Rieux-Laucat
Hôpital Necker INSERM U429, Paris, France
Cell Death Differ 10:124-33. 2003..This review will discuss the main findings provided by the study of mouse models and human conditions...
- Lymphoproliferative syndrome with autoimmunity: A possible genetic basis for dominant expression of the clinical manifestationsF Rieux-Laucat
Department of Pediatric Immunology, Unit INSERM U429, Hopital Necker Enfants Malades, Paris, France
Blood 94:2575-82. 1999..This observation suggests that Fas-mediated apoptosis plays a more important role in lymphocyte homeostasis in early childhood than later on in life...
- Autoimmune lymphoproliferative syndrome with somatic Fas mutationsEliska 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...
- 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 cellsAnne 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...
- Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytesVéronique 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...
- Differential sensitivity of Jurkat and primary T cells to caspase-independent cell death triggered upon Fas stimulationCedric Vonarbourg
INSERM U429, Developpement Normal et Pathologique du Systeme Immunitaire, Hopital Necker Enfants Malades, Paris, France
Eur J Immunol 32:2376-84. 2002..Indeed, in this setting, Fas-induced cell death was always substantially inhibited by Z-VAD-fmk, suggesting that caspase activation is an absolute requirement in the Fas-induced death of primary human T lymphocytes...
- A Mendelian predisposition to B-cell lymphoma caused by IL-10R deficiencyBenedicte Neven
Unité d Immuno Hématologie Pédiatrique, Hopital Necker Enfant Malades, Assistance publique des Hôpitaux de Paris APHP, Paris, France
Blood 122:3713-22. 2013..Hence, IL-10R deficiency is associated with a high risk of developing B-cell lymphoma. Our results revealed an unexpected role of the IL-10R pathway in lymphomagenesis. ..
- Somatic loss of heterozygosity, but not haploinsufficiency alone, leads to full-blown autoimmune lymphoproliferative syndrome in 1 of 12 family members with FAS start codon mutationFabian Hauck
Inserm U768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Hopital Necker Enfants Malades, Paris, France
Clin Immunol 147:61-8. 2013..FAS surface expression on DN T cells should be assessed routinely and FAS haploinsufficient patients should be followed as its potential for lymphomagenesis is not well defined and a second hit might occur later on...
- Efficacy of gene therapy for X-linked severe combined immunodeficiencySalima 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...
- Reduced expression of FOXP3 and regulatory T-cell function in severe forms of early-onset autoimmune enteropathyNicolette 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...
- Defective IL10 signaling defining a subgroup of patients with inflammatory bowel diseaseBernadette Begue
INSERM U989, Paris, France
Am J Gastroenterol 106:1544-55. 2011..Thus, we aimed to further elaborate the hypothesis of defective anti-inflammatory responses in patients with IBD...
- STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunityCapucine 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...
- Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutationAude Magerus-Chatinet
Unité Inserm 768, Hopital Necker Enfants Malades, Paris, France
J Allergy Clin Immunol 131:486-90. 2013..Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphoproliferation, accumulation of double-negative T cells, hypergammaglobulinemia G and A, and autoimmune cytopenia...
- A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutationBenedicte Neven
Inserm U768, Hopital Necker Enfants Malades, Paris, France
Blood 118:4798-807. 2011..We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients...
- Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulationAude Magerus-Chatinet
Inserm U768, Universite Paris Descartes, Hopital Necker Enfants Malades, Paris, France
J Clin Invest 121:106-12. 2011..This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases...
- Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patientsBenedicte Neven
Unité d Immuno Hématologie Pédiatrique, Hopital Necker Enfant Malades, Assistance Publique des Hopitaux de Paris, Paris, France Développement normal et pathologique du système immunitaire, Unité INSERM U768, Université Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France
Blood 124:1597-609. 2014..Similar observations were made in spleens of fas-deficient mice. Our data revealed an unexpected mechanism by which ALPS results in anti-polysaccharide IgM antibody production-specific defect. Splenectomy should be avoided. ..
- Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working GroupBenedicte Pigneur
Universite Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France Assistance Publique Hôpitaux de Paris, Hopital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France Department of Pediatric Gastroenterology, ErasmusMC Sophia Children s Hospital, Rotterdam, The Netherlands Department of Gastroenterology, Great Ormond Street Hospital for Sick Children and Institute of Child Health, London, United Kingdom Pediatric Gastroenterology Unit, Centro Hospitalar do Porto, Porto, Portugal Marienhospital, Bonn, Germany Department of Gastroenterology, Hepatology and Feeding Disorders, The Children s Memorial Health Institute, Warsaw, Poland Gastroenterologia, Endoscopia Digestiva, Epatologia e Cura del Bambino con Trapianto di Fegato, Dipartimento Salute della Donna e del Bambino, Padova, Italy Assistance Publique Hôpitaux de Paris, Hopital Necker Enfants Malades, Service d Anatomopathologie, Paris, France Assistance Publique Hôpitaux de Paris, Hopital Necker Enfants Malades, Service de Radiologie, Paris, France Inserm U989, Paris, Turkey
Inflamm Bowel Dis 19:2820-8. 2013..We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution...
- Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiencyFabian Hauck
Inserm 768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Hopital Necker Enfants Malades, Paris, France
J Allergy Clin Immunol 130:1144-1152.e11. 2012..The T lymphocyte-specific protein tyrosine kinase (Lck) is a key component of the TCR signaling machinery. On the basis of its function, we considered LCK a candidate gene in patients with combined immunodeficiency...
- Hypomorphic mutation of ZAP70 in human results in a late onset immunodeficiency and no autoimmunityCapucine 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...
- 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 functionAude 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...
- Digestive histopathological presentation of IPEX syndromeNatacha Patey-Mariaud de Serre
Department of Pathology, Necker Enfants Malades, Universite Rene Descartes Paris V, tumorothèque, Paris, France
Mod Pathol 22:95-102. 2009....
- MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survivalNadine T Nehme
Inserm U768, Paris, France
Blood 119:3458-68. 2012..Our results characterize a new mechanism in primary T-cell immunodeficiencies and highlight a role of the MST1/FOXO1 pathway in controlling the death of human naive T cells...
- Accessory spleen: differential diagnosis for lymphoma in autoimmune lymphoproliferative syndromeSophie Georgin-Lavialle
Department of Adult Hematology, Hopital Necker, Universite Paris Descartes, Faculte de Medecine, Assistance Publique Hopitaux de Paris, Paris, France
Pediatr Blood Cancer 54:1020-2. 2010..This observation highlights the lymphoma's differential diagnosis in this context...
- XIAP deficiency in humans causes an X-linked lymphoproliferative syndromeStéphanie Rigaud
Inserm 768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Univ René Descartes, Paris, F 75015, France
Nature 444:110-4. 2006..Furthermore, by identifying an XLP immunodeficiency that is caused by mutations in XIAP, we show that XIAP is a potent regulator of lymphocyte homeostasis in vivo...
- Clinical and molecular aspects of autoimmune enteropathy and immune dysregulation, polyendocrinopathy autoimmune enteropathy X-linked syndromeFrank M Ruemmele
AP HP, Hopital Necker Enfants Malades, Department of Pediatrics, Pediatric Gastroenterology Unit, France
Curr Opin Gastroenterol 24:742-8. 2008..Recent research data allowed us to gain a first insight in the pathogenesis of AIE. On the basis of this data, we will discuss new aspects of AIE emphasizing new diagnostic and therapeutic possibilities...
- Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiencyRoxane Lemoine
INSERM, Unité U1163, Laboratoire Homéostasie normale et pathologique du système immunitaire, Hopital Necker Enfants Malades, Paris, France Université Paris Descartes Sorbonne Paris Cité, Institut Imagine, Paris, France Unité d Immunologie et Hématologie Pédiatrique, Assistance Publique Hopitaux de Paris, Hopital Necker Enfants Malades, Paris, France
J Allergy Clin Immunol 134:1354-1364.e6. 2014..Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases, but the underlying molecular mechanisms remain largely unknown. Studies of monogenic diseases can provide insight into the pathogenesis of IBD...
- Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicityChantal 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....
- Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafnessChantal 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...