Fulminant Viral Hepatitis in Two Siblings with Inherited IL-10RB Deficiency

• DOI: 10.1007/s10875-022-01376-5
• Publication Date: 2022-10-29T04:02:37Z
• Authors: Cecilia B. Korol; Serkan Belkaya; Fahad Alsohime; Lazaro Lorenzo; Stéphanie Boisson...; Joseph Brancale; Anna-Lena Neehus; Silvia Vilarinho; Alsum Zobaida; Rabih Halwani; Saleh Al-Muhsen; Jean-Laurent Casa...; Emmanuelle Jouanguy
• Keywords: Fulminant; Liver disease; Fulminant hepatitis

Abstract Fulminant viral hepatitis (FVH) caused by A virus (HAV) is a life-threatening disease that typically strikes otherwise healthy individuals. The only known genetic etiology of FVH inherited IL-18BP deficiency, which unleashes IL-18-dependent lymphocyte cytotoxicity and IFN-γ production. We studied two siblings who died from combination early-onset inflammatory bowel (EOIBD) due to HAV. sibling tested was homozygous for the W100G variant IL10RB previously described in an unrelated patient with EOIBD. show here out-of-frame variants seen other EOIBD patients disrupt cellular responses IL-10, IL-22, IL-26, IFN-λs overexpression conditions cells. By contrast, impact in-frame disease-causing varies between cases. When overexpressed, impairs but not or IFN-λ1, whereas cells do respond IFN-λ1. As IL-10 potent antagonist phagocytes, these findings suggest molecular basis IL-10RB deficiency may involve excessive activity during HAV infections liver. Inherited possibly IL-10RA deficiencies, confer predisposition FVH, deficiencies should be vaccinated against liver-tropic viruses.