title: The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood.
abstract: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.
authors.affiliation: Department of Pediatrics, UFMG, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: Priscila Menezes
authors.identifier: 0000-0002-8608-8503
authors.initials: PM
authors.lastname: Ferri
authors.affiliation: Department of Pediatrics, UFMG, 30130-100 Belo Horizonte, MG, Brazil; Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, INCT-MM, CNPq-FAPEMIG, Universidade Federal de Minas Gerais, 30130-100 Belo Horizonte, MG, Brazil; Laboratório Interdisciplinar de Investigação Médica, Avenida Alfredo Balena 190, 2nd Floor, Room 281, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: Ana Cristina
authors.identifier: 0000-0001-9222-3882
authors.initials: AC
authors.lastname: Simões E Silva
authors.affiliation: Department of Pediatrics, UFMG, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: Soraya Luiza
authors.initials: SL
authors.lastname: Campos Silva
authors.affiliation: Department of Pediatrics, UFMG, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: Diego Junior Queiroga
authors.identifier: 0000-0002-7093-543X
authors.initials: DJ
authors.lastname: de Aquino
authors.affiliation: Department of Pediatrics, UFMG, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: Eleonora Druve Tavares
authors.identifier: 0000-0002-5671-9570
authors.initials: ED
authors.lastname: Fagundes
authors.affiliation: Department of Pediatrics, UFMG, 30130-100 Belo Horizonte, MG, Brazil; Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, INCT-MM, CNPq-FAPEMIG, Universidade Federal de Minas Gerais, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Marques de Miranda
authors.affiliation: Department of Pediatrics, UFMG, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: Alexandre Rodrigues
authors.initials: AR
authors.lastname: Ferreira