Inborn errors of type I interferon immunity in patients with symptomatic acute hepatitis E.

Autor:	Saadat A; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Gouttenoire J; Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Ripellino P; Department of Neurology, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland., Semela D; Division of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen, Switzerland., Amar S; Swiss Transfusion, Swiss Red Cross, Bern, Switzerland., Frey BM; Blood Transfusion Service SRC, Schlieren/Zurich, Switzerland., Fontana S; Swiss Transfusion, Swiss Red Cross, Bern, Switzerland., Mdawar-Bailly E; Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Moradpour D; Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Fellay J; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; Swiss Institute of Bioinformatics, Lausanne, Switzerland.; Precision Medicine Unit, Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Fraga M; Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2024 Jun 01; Vol. 79 (6), pp. 1421-1431. Date of Electronic Publication: 2023 Dec 08.
DOI:	10.1097/HEP.0000000000000701
Abstrakt:	Background and Aims: The clinical spectrum of human infection by HEV ranges from asymptomatic to severe acute hepatitis. Furthermore, HEV can cause diverse neurological manifestations, especially Parsonage-Turner syndrome. Here, we used a large-scale human genomic approach to search for genetic determinants of severe clinical presentations of HEV infection. Approach and Results: We performed whole genome sequencing in 3 groups of study participants with PCR-proven acute HEV infection: (1) 24 patients with symptomatic acute hepatitis E; (2) 12 patients with HEV-associated Parsonage-Turner syndrome; and (3) 16 asymptomatic blood donors (controls). For variant calling and annotation, we used GATK4 best practices followed by Variant Effect Predictor (VEP) and Annovar. For variant classification, we implemented the American College of Medical Genetics and Genomics/Association for Molecular Pathology Bayesian classification framework in R. Variants with a probability of pathogenicity >0.9 were considered damaging. We used all genes with at least 1 damaging variant as input for pathway enrichment analyses.We observed a significant enrichment of type I interferon response pathways in the symptomatic hepatitis group: 10 out of 24 patients carried a damaging variant in one of 9 genes encoding either intracellular viral sensors ( IFIH1 , DDX58 , TLR3 , POLR3B , POLR3C ) or other molecules involved in type I interferon response [interferon regulatory factor 7 ( IRF7 ), MYD88 , OAS3 , GAPDH ]. We did not find any enriched pathway in the Parsonage-Turner syndrome group or in the controls. Conclusions: Our results highlight the essential role of type I interferon in preventing symptomatic acute hepatitis E. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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