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Signatures of AAV-2 immunity are enriched in children with severe acute hepatitis of unknown etiology

Moriah Mitchell, Yumei Leng, Suresh B. Boppana, William J. Britt, Luz Helena Gutierrez Sanchez, Stephen J. Elledge

2023Science Translational Medicine10 citationsDOIOpen Access PDF

Abstract

Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a clear cause for the liver damage observed in these cases remains to be identified. Using VirScan, a high-throughput antibody profiling technology, we probed the antibody repertoires of nine cases of severe acute hepatitis of unknown etiology treated at Children's of Alabama and compared their antibody responses with 38 pediatric and 470 adult controls. We report increased adeno-associated dependoparvovirus A (AAV-A) breadth in cases relative to controls and adeno-associated virus 2 (AAV-2) peptide responses that were conserved in seven of nine cases but rarely observed in pediatric and adult controls. These findings suggest that AAV-2 is a likely etiologic agent of severe acute hepatitis of unknown etiology.

Topics & Concepts

EtiologyMedicineAntibodyImmunologyImmunityVirusHepatitisHepatitis a virusImmune systemInternal medicineVirus-based gene therapy researchAnimal Virus Infections StudiesViral gastroenteritis research and epidemiology