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Late-onset enteric virus infection associated with hepatitis (EVAH) in transplanted SCID patients.
Riller, Quentin; Fourgeaud, Jacques; Bruneau, Julie; De Ravin, Suk See; Smith, Grace; Fusaro, Mathieu; Meriem, Samy; Magerus, Aude; Luka, Marine; Abdessalem, Ghaith; Lhermitte, Ludovic; Jamet, Anne; Six, Emmanuelle; Magnani, Alessandra; Castelle, Martin; Lévy, Romain; Lecuit, Mathilde M; Fournier, Benjamin; Winter, Sarah; Semeraro, Michaela; Pinto, Graziella; Abid, Hanène; Mahlaoui, Nizar; Cheikh, Nathalie; Florkin, Benoit; Frange, Pierre; Jeziorski, Eric; Suarez, Felipe; Sarrot-Reynauld, Françoise; Nouar, Dalila; Debray, Dominique; Lacaille, Florence; Picard, Capucine; Pérot, Philippe; Regnault, Béatrice; Da Rocha, Nicolas; de Cevins, Camille; Delage, Laure; Pérot, Brieuc P; Vinit, Angélique; Carbone, Francesco; Brunaud, Camille; Marchais, Manon; Stolzenberg, Marie-Claude; Asnafi, Vahid; Molina, Thierry; Rieux-Laucat, Frédéric; Notarangelo, Luigi D; Pittaluga, Stefania; Jais, Jean Philippe.
  • Riller Q; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Fourgeaud J; University of Paris Cité, Paris, France; Microbiology Department, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, France; Prise en Charge des Anomalies Congénitales et leur Traitement, Unit
  • Bruneau J; University of Paris Cité, Paris, France; Pathology Department, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Imagine Institute, INSERM UMR 1163, Laboratory of Molecular Mechanisms of Hematologic Disorders and Therapeutic Implications, Necker-Children's Hospital, A
  • De Ravin SS; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
  • Smith G; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md.
  • Fusaro M; Study Center for Primary Immunodeficiencies, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Meriem S; Laboratory of Biostatistics, University of Paris Cité, Paris, France.
  • Magerus A; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Luka M; Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Abdessalem G; Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Lhermitte L; University of Paris Cité, Paris, France; Laboratory of Onco-Haematology, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; the Institut Necker-Enfants Malades (INEM), INSERM UMR 1151, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Jamet A; University of Paris Cité, Paris, France; Microbiology Department, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; the Institut Necker-Enfants Malades (INEM), INSERM UMR 1151, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Six E; University of Paris Cité, Paris, France; Laboratory of Human Lympho-Hematopoiesis, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Magnani A; Department of Biotherapy, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Castelle M; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Lévy R; University of Paris Cité, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker-Children's Hospital, Assistance Publiqu
  • Lecuit MM; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Fournier B; University of Paris Cité, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Winter S; University of Paris Cité, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Semeraro M; University of Paris Cité, Paris, France; Clinical Investigation Center, Clinical Research Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Pinto G; Pediatric Endocrinology, Gynecology, Diabetology, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Abid H; University of Paris Cité, Paris, France; Microbiology Department, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Mahlaoui N; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Cheikh N; Pediatric Hematology Oncology Unit, University Hospital of Besançon, Besançon, France.
  • Florkin B; Immuno-Hémato-Rhumatologie Pédiatrique, Service de Pédiatrie, CHR Citadelle, Liege, Belgium.
  • Frange P; University of Paris Cité, Paris, France; Microbiology Department, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Jeziorski E; Department of Pediatrics, Infectious Diseases, and Immunology, University of Montpellier, CHU Montpellier, Montpellier, France.
  • Suarez F; University of Paris Cité, Paris, France; Imagine Institute, INSERM UMR 1163, Laboratory of Molecular Mechanisms of Hematologic Disorders and Therapeutic Implications, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Hematology Department, Necker-Children's Hospital,
  • Sarrot-Reynauld F; Service de Médecine Interne, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
  • Nouar D; Service d'Immunologie Clinique et d'Allergologie, Centre Hospitalier Régional Universitaire, Tours, France.
  • Debray D; Pediatric Liver Unit, National Reference Center for Rare Diseases, Biliary Atresia and Genetic Cholestasis, Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare Liver, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Lacaille F; Gastroenterology-Hepatology-Nutrition Unit, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Picard C; Study Center for Primary Immunodeficiencies, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Pérot P; Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, France; OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Institut Pasteur, Paris, France.
  • Regnault B; Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, France; OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Institut Pasteur, Paris, France.
  • Da Rocha N; Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, France; OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Institut Pasteur, Paris, France.
  • de Cevins C; University of Paris Cité, Paris, France; Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, Imagine Institute, INSERM UMR 1163, Paris, France; Artificial Intelligence & Deep Analytics (AIDA) Group, Data & Data Science (DDS), Sanofi R&D, Chilly
  • Delage L; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Pérot BP; University of Paris Cité, Paris, France; Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Vinit A; Sorbonne Université, UMS037, PASS, Plateforme de Cytométrie de la Pitié-Salpêtrière CyPS, Paris, France.
  • Carbone F; University of Paris Cité, Paris, France; Labtech Single-Cell@Imagine, Imagine Institute, INSERM UMR 1163, Paris, France; Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Brunaud C; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Marchais M; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Stolzenberg MC; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Asnafi V; University of Paris Cité, Paris, France; Laboratory of Onco-Haematology, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; the Institut Necker-Enfants Malades (INEM), INSERM UMR 1151, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Molina T; University of Paris Cité, Paris, France; Pathology Department, Necker-Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Rieux-Laucat F; University of Paris Cité, Paris, France; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR 1163, Paris, France.
  • Notarangelo LD; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
  • Pittaluga S; National Cancer Institute, National Institutes of Health, Bethesda, Md.
  • Jais JP; University of Paris Cité, Paris, France; Laboratory of Biostatistics, University of Paris Cité, Paris, France.
J Allergy Clin Immunol ; 151(6): 1634-1645, 2023 06.
Article en En | MEDLINE | ID: mdl-36638922
ABSTRACT

BACKGROUND:

Allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are potentially curative treatments for severe combined immunodeficiency (SCID). Late-onset posttreatment manifestations (such as persistent hepatitis) are not uncommon.

OBJECTIVE:

We sought to characterize the prevalence and pathophysiology of persistent hepatitis in transplanted SCID patients (SCIDH+) and to evaluate risk factors and treatments.

METHODS:

We used various techniques (including pathology assessments, metagenomics, single-cell transcriptomics, and cytometry by time of flight) to perform an in-depth study of different tissues from patients in the SCIDH+ group and corresponding asymptomatic similarly transplanted SCID patients without hepatitis (SCIDH-).

RESULTS:

Eleven patients developed persistent hepatitis (median of 6 years after HSCT or GT). This condition was associated with the chronic detection of enteric viruses (human Aichi virus, norovirus, and sapovirus) in liver and/or stools, which were not found in stools from the SCIDH- group (n = 12). Multiomics analysis identified an expansion of effector memory CD8+ T cells with high type I and II interferon signatures. Hepatitis was associated with absence of myeloablation during conditioning, split chimerism, and defective B-cell function, representing 25% of the 44 patients with SCID having these characteristics. Partially myeloablative retransplantation or GT of patients with this condition (which we have named as "enteric virus infection associated with hepatitis") led to the reconstitution of T- and B-cell immunity and remission of hepatitis in 5 patients, concomitantly with viral clearance.

CONCLUSIONS:

Enteric virus infection associated with hepatitis is related to chronic enteric viral infection and immune dysregulation and is an important risk for transplanted SCID patients with defective B-cell function.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Virosis / Inmunodeficiencia Combinada Grave / Trasplante de Células Madre Hematopoyéticas / Infecciones por Enterovirus / Hepatitis Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Virosis / Inmunodeficiencia Combinada Grave / Trasplante de Células Madre Hematopoyéticas / Infecciones por Enterovirus / Hepatitis Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article