1. Chronic Aichi Virus Infection As a Cause of Long-Lasting Multiorgan Involvement in Patients With Primary Immune Deficiencies
- Author
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Jacques Fourgeaud, Mathilde M Lecuit, Philippe Pérot, Julie Bruneau, Beatrice Regnault, Nicolas Da Rocha, Mael Bessaud, Capucine Picard, Éric Jeziorski, Benjamin Fournier, Romain Levy, Ambroise Marçais, Stéphane Blanche, Pierre Frange, Alain Fischer, Marina Cavazzana, Agnès Ferroni, Anne Jamet, Marianne Leruez-Ville, Marc Eloit, Bénédicte Neven, Fédération pour la recherche en explorations et thérapeutiques innovantes in utéro (FETUS (URP 7328)), Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Signalisation antivirale - Virus sensing and signaling, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Activation lymphocytaire et susceptibilité au virus d’Epstein-Barr = Lymphocyte activation and susceptibility to EBV, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Collège de France (CdF (institution)), Human Lymphohematopoiesis Laboratory (Equipe Inserm U1163), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École nationale vétérinaire - Alfort (ENVA), and This work was supported by the Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Institut Pasteur and the Necker-Enfants malades University Hospital.
- Subjects
Microbiology (medical) ,Aichi virus ,Infectious Diseases ,X-linked agammaglobulinemia ,Primary Immune Deficiency ,[SDV]Life Sciences [q-bio] ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,chronic hepatitis ,Metagenomic Next generation sequencing ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background Metagenomic next-generation sequencing (mNGS) was used to assess patients with primary or secondary immune deficiencies (PIDs and SIDs) who presented with immunopathological conditions related to immunodysregulation. Methods Thirty patients with PIDs or SIDs who presented with symptoms related to immunodysregulation and 59 asymptomatic patients with similar PIDs or SIDs were enrolled. mNGS was performed on organ biopsy. Specific Aichi virus (AiV) reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm AiV infection and screen the other patients. In situ hybridization (ISH) assay was done on AiV-infected organs to identify infected cells. Virus genotype was determined by phylogenetic analysis. Results AiV sequences were detected using mNGS in tissue samples of 5 patients and by RT-PCR in peripheral samples of another patient, all of whom presented with PID and long-lasting multiorgan involvement, including hepatitis, splenomegaly, and nephritis in 4 patients. CD8+ T-cell infiltration was a hallmark of the disease. RT-PCR detected intermittent low viral loads in urine and plasma from infected patients but not from uninfected patients. Viral detection stopped after immune reconstitution obtained by hematopoietic stem cell transplantation. ISH demonstrated the presence of AiV RNA in hepatocytes (n = 1) and spleen tissue (n = 2). AiV belonged to genotype A (n = 2) or B (n = 3). Conclusions The similarity of the clinical presentation, the detection of AiV in a subgroup of patients suffering from immunodysregulation, the absence of AiV in asymptomatic patients, the detection of viral genome in infected organs by ISH, and the reversibility of symptoms after treatment argue for AiV causality.
- Published
- 2023