Genomic investigations of unexplained acute hepatitis in children

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

Sacrosancti Et Oecumenici Concilii Tridentini Paulo III. Iulio III. Et Pio IV. Pont. Max. celebrati, Canones Et Decreta

Layoutgetreues Digitalisat der Ausg.: Coloniae : Gualtherus, 1610 Standort: Bibliothek Religionswissenschaft (510) Signatur: 207 Bemerkungen: Nachweis alter Drucke: VD17 12:124028G (Bibliothek Wittgenstein

Die Bulle: In Coena Domini, von Pabst Paul dem Dritten im Jahre 1536. Zur Erlauterung der neuesten Streitigkeiten des Roemischen Hofes. Aus dem Lateinischen nach dem Original uebersetzt.

DIE BULLE: IN COENA DOMINI, VON PABST PAUL DEM DRITTEN IM JAHRE 1536. ZUR ERLAUTERUNG DER NEUESTEN STREITIGKEITEN DES ROEMISCHEN HOFES. AUS DEM LATEINISCHEN NACH DEM ORIGINAL UEBERSETZT. Die Bulle: In Coena Domini, von Pabst Paul dem Dritten im Jahre 1536. Zur Erlauterung der neuesten Streitigkeiten des Roemischen Hofes. Aus dem Lateinischen nach dem Original uebersetzt. (2) Titelseite (2) Die Bulle: In Coena Domini, von Pabst Paul dem Dritten im Jahre 1536 (3

Sacrosancti Et Oecumenici Concilii Tridentini Paulo III. Iulio III. Et Pio IV. Pont. Max. celebrati, Canones Et Decreta

Layoutgetreues Digitalisat der Ausg.: Coloniae : Gualtherus, 1610 Standort: Bibliothek Religionswissenschaft (510) Signatur: 207 Bemerkungen: Nachweis alter Drucke: VD17 12:124028G (Bibliothek Wittgenstein