Combined germline and somatic human FADD mutations cause autoimmune lymphoproliferative syndrome.

Autor:	Pellé O; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Moreno S; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Lorenz MR; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Riller Q; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Fuehrer M; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service Baden-Wuerttemberg-Hessen, Ulm, Germany; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Stolzenberg MC; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Maccari ME; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Lenoir C; University of Paris Cité, Paris, France; Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Cheminant M; Clinical Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; French National Reference Centre for Primary Immunodeficiencies (CEREDIH), Paris, France., Hinze T; Department of Pediatric Rheumatology and Immunology, University Hospital Münster, Münster, Germany., Hebart HF; Department of Internal Medicine, Kliniken Ostalb, Stauferklinikum, Mutlangen, Germany., König C; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany., Schvartz A; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Schmitt Y; University of Paris Cité, Paris, France; Genomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 and INSERM US24/CNRS UAR3633, Paris, France., Vinit A; Sorbonne Université, UMS037, PASS, Plateforme de Cytométrie de la Pitié-Salpêtrière CyPS, Paris, France., Henry E; Genomics Platform, Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, Paris, France., Touzart A; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Institut Necker-Enfants Malades (INEM), INSERM U1151, Paris, France., Villarese P; Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Institut Necker-Enfants Malades (INEM), INSERM U1151, Paris, France., Isnard P; Institut Necker-Enfants Malades (INEM), INSERM U1151, Paris, France; Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France., Neveux N; Laboratory of Biological Nutrition, Faculty of Pharmacy, Paris University, Paris, France; Clinical Chemistry Department, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France., Landman-Parker J; Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP) Armand Trousseau, Paris, France., Picard C; University of Paris Cité, Paris, France; Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Imagine Institute, INSERM UMR 1163, Paris, France; Study Center for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Fouyssac F; Pediatric Oncology and Hematology Unit, Children Hospital, Vandoeuvre-les-Nancy, Paris, France., Neven B; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Pediatric Immuno-hematology and Rheumatology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Grimbacher B; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Speckmann C; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Fischer A; University of Paris Cité, Paris, France; Pediatric Immuno-hematology and Rheumatology Department, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France; Collège de France, Paris, France., Latour S; University of Paris Cité, Paris, France; Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France., Schwarz K; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service Baden-Wuerttemberg-Hessen, Ulm, Germany., Ehl S; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Rieux-Laucat F; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France. Electronic address: frederic.rieux-laucat@inserm.fr., Rensing-Ehl A; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Magérus A; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France; Imagine Institute, INSERM UMR 1163, Paris, France. Electronic address: aude.magerus@inserm.fr.
Jazyk:	angličtina
Zdroj:	The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2024 Jan; Vol. 153 (1), pp. 203-215. Date of Electronic Publication: 2023 Oct 02.
DOI:	10.1016/j.jaci.2023.09.028
Abstrakt:	Background: The autoimmune lymphoproliferative syndrome (ALPS) is a noninfectious and nonmalignant lymphoproliferative disease frequently associated with autoimmune cytopenia resulting from defective FAS signaling. We previously described germline monoallelic FAS (TNFRSF6) haploinsufficient mutations associated with somatic events, such as loss of heterozygosity on the second allele of FAS, as a cause of ALPS-FAS. These somatic events were identified by sequencing FAS in DNA from double-negative (DN) T cells, the pathognomonic T-cell subset in ALPS, in which the somatic events accumulated. Objective: We sought to identify whether a somatic event affecting the FAS-associated death domain (FADD) gene could be related to the disease onset in 4 unrelated patients with ALPS carrying a germline monoallelic mutation of the FADD protein inherited from a healthy parent. Methods: We sequenced FADD and performed array-based comparative genomic hybridization using DNA from sorted CD4 + or DN T cells. Results: We found homozygous FADD mutations in the DN T cells from all 4 patients, which resulted from uniparental disomy. FADD deficiency caused by germline heterozygous FADD mutations associated with a somatic loss of heterozygosity was a phenocopy of ALPS-FAS without the more complex symptoms reported in patients with germline biallelic FADD mutations. Conclusions: The association of germline and somatic events affecting the FADD gene is a new genetic cause of ALPS. (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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