Inherited IL-18BP deficiency in human fulminant viral hepatitis

• DOI: 10.1084/jem.20190669
• Publication Date: 2019-06-18T18:35:15Z
• Authors: Serkan Belkaya; Eleftherios Micha...; Cecilia B. Korol; Mohammad Kabbani; Aurélie Cobat; Paul Bastard; Yoon Seung Lee; Nicholas Hernandez; Scott Drutman; Ype P. de Jong; Eric Vivier; Julie Bruneau; Vivien Béziat; Bertrand Boisson; Lazaro Lorenzo-Diaz; Soraya Boucherit; Mylène Sebagh; Emmanuel Jacquemin; Jean-François Emile; Laurent Abel; Charles M. Rice; Emmanuelle Jouanguy; Jean-Laurent Casa...
• Keywords: Fulminant; Fulminant hepatitis

Fulminant viral hepatitis (FVH) is a devastating and unexplained condition that strikes otherwise healthy individuals during primary infection with common liver-tropic viruses. We report child who died of FVH upon A virus (HAV) at age 11 yr was homozygous for private 40-nucleotide deletion in IL18BP, which encodes the IL-18 binding protein (IL-18BP). This mutation loss-of-function, unlike variants found state public databases. show human IL-18BP are both secreted mostly by hepatocytes macrophages liver. Moreover, absence IL-18BP, excessive NK cell activation results uncontrolled killing vitro. Inherited deficiency thus underlies fulminant HAV unleashing IL-18. These findings provide proof-of-principle can be caused single-gene inborn errors selectively disrupt liver-specific immunity. They also toxic to liver its antidote.