26 research outputs found
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
Characterization of the novel HLA-DQA1*01:58 allele by sequencing-based typing
HLA-DQA1*01:58 differs from HLA-DQA1*01:02:01:06 by one nucleotide substitution in codon 46 in exon 2
Characterization of the novel HLA-DQA1*01:02:11 allele by sequencing-based typing
HLA-DQA1*01:02:11 differs from HLA-DQA1*01:02:01:10 by one nucleotide substitution in codon 201 in exon 4
Characterization of the novel HLA-DPA1*01:42 allele by sequencing-based typing
HLA-DPA1*01:42 differs from DPA1*01:03:01:02 by one nucleotide substitution in Codon 76 in Exon 2
Characterization of the novel HLA-DPA1*01:60 allele by sequencing-based typing
HLA-DPA1*01:60 differs from HLA-DPA1*01:03:01:04 by one nucleotide substitution in codon 224 in exon 4
Characterization of the novel HLA-DPA1*01:44 allele by sequencing-based typing
HLA-DPA1*01:44 differs from DPA1*01:03:01:04 by one nucleotide substitution in codon 175 in exon 3
Characterization of the novel HLA-DPA1*01:61 allele by sequencing-based typing
HLA-DPA1*01:61 differs from HLA-DPA1*01:03:01:22 by one nucleotide substitution in codon 96 in exon 3
Characterization of the novel HLA-DRB3*03:49 allele by sequencing-based typing
HLA-DRB3*03:49 differs from DRB3*03:01:01:01 by one nucleotide substitution in codon 191 in exon 4
Characterization of the novel HLA‐DQA1*03:20 allele by sequencing‐based typing
HLA-DQA1*03:20 differs from HLA-DQA1*03:03:01:01 by one nucleotide substitution in codon 33 in exon 2