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SHR Neuro Cancer Cardio Lipid Metab Microb
Morfopoulou, S; Buddle, S; Torres, Montaguth, OE; Atkinson, L; Guerra-Assunção, JA; Moradi, Marjaneh, M; Zennezini, Chiozzi, R; Storey, N; Campos, L; Hutchinson, JC; Counsell, JR; Pollara, G; Roy, S; Venturini, C; Antinao, Diaz, JF; Siam, A; Tappouni, LJ; Asgarian, Z; Ng, J; Hanlon, KS; Lennon, A; McArdle, A; Czap, A; Rosenheim, J; Andrade, C; Anderson, G; Lee, JCD; Williams, R; Williams, CA; Tutill, H; Bayzid, N; Martin, Bernal, LM; Macpherson, H; Montgomery, KA; Moore, C; Templeton, K; Neill, C; Holden, M; Gunson, R; Shepherd, SJ; Shah, P; Cooray, S; Voice, M; Steele, M; Fink, C; Whittaker, TE; Santilli, G; Gissen, P; Kaufer, BB; Reich, J; Andreani, J; Simmonds, P; Alrabiah, DK; Castellano, S; Chikowore, P; Odam, M; Rampling, T; Houlihan, C; Hoschler, K; Talts, T; Celma, C; Gonzalez, S; Gallagher, E; Simmons, R; Watson, C; Mandal, S; Zambon, M; Chand, M; Hatcher, J; De, S; Baillie, K; Semple, MG; Martin, J; Ushiro-Lumb, I; Noursadeghi, M; Deheragoda, M; Hadzic, N; Grammatikopoulos, T; Brown, R; Kelgeri, C; Thalassinos, K; Waddington, SN; Jacques, TS; Thomson, E; Levin, M; Brown, JR; Breuer, J; DIAMONDS Consortium; PERFORM Consortium; ISARIC 4C Investigators.
Genomic investigations of unexplained acute hepatitis in children.
Nature. 2023; 617(7961): 564-573.
Doi: 10.1038/s41586-023-06003-w
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- Study Group Members Med Uni Graz:
- Bauchinger Sebastian
- Baumgart Hinrich
- Benesch Martin
- Binder Alexander
- Eber Ernst
- Gallistl Siegfried
- Gores Gunther
- Haidl Harald
- Hauer Almuthe
- Keldorfer Markus
- Kohlfürst Daniela
- Kohlmaier Benno
- Krenn Larissa
- Leitner Manuel
- Löffler Sabine
- Niedrist Tobias Josef
- Nordberg Gudrun
- Pfleger Andreas
- Pfurtscheller Klaus
- Pilch Heidemarie
- Pölz Lena
- Rajic Glorija
- Roedl Siegfried
- Sagmeister Manfred Gerald
- Schweintzger Nina
- Skrabl-Baumgartner Andrea
- Sperl Matthias
- Stampfer Laura
- Strenger Volker
- Till Holger
- Trobisch Andreas
- Zenz Werner
- Zurl Christoph Johann
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- Abstract:
- Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.
- Find related publications in this database (using NLM MeSH Indexing)
- Child - administration & dosage
- Humans - administration & dosage
- Acute Disease - epidemiology
- Adenovirus Infections, Human - epidemiology, immunology, virology
- B-Lymphocytes - immunology
- Gene Expression Profiling - administration & dosage
- Genomics - administration & dosage
- Hepatitis - epidemiology, immunology, virology
- Immunohistochemistry - administration & dosage
- Liver - immunology, virology
- Proteomics - administration & dosage
- T-Lymphocytes - immunology