title: Autoimmune Hepatitis in Brazilian Children: IgE and Genetic Polymorphisms in Associated Genes.
abstract: Pediatric autoimmune hepatitis (AIH) patients present hypergammaglobulinemia, periportal CD8(+) cytotoxic T cell infiltration, and cirrhosis. Autoantibody profile defines AIH types 1 and 2 in addition to strong association with HLA-DRB1. We previously detected increased IgE serum levels and sought to compare clinical and histological features according to IgE levels in AIH (n = 74, ages 1-14 years) patients. Additionally, we typed 117 patients and 227 controls for functional polymorphisms of IL4, IL13, IL5, and IL4RA genes involved in IgE switching and eosinophil maturation that might contribute to overall genetic susceptibility to AIH. Serum IgE levels were high in 55% of AIH-1, but only in 12% of AIH-2 (P = 0.003) patients. Liver IgE was present in 91.3% of AIH-1 patients. The A alleles at both IL13 rs20541 and IL4RA rs1805011 were associated with AIH-1 (P = 0.024, OR = 1.55 and P < 0.0001, OR = 2.15, resp.). Furthermore, individuals presenting homozygosis for the A allele at IL4RA rs1805011 and HLA-DRB1(∗)03 and/or (∗)13 allele had sixfold greater risk to develop the disease (OR = 14.00, P < 0.001). The novel association suggests an additional role for IgE-linked immune response genes in the pathogenesis of AIH.
authors.affiliation: Laboratório de Medicina Laboratorial (LIM03), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Léa Campos
authors.initials: LC
authors.lastname: de Oliveira
authors.affiliation: Hospital Israelita Albert Einstein, 05652-900 São Paulo, SP, Brazil ; Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia, 05403-000 São Paulo, SP, Brazil.
authors.forename: Anna Carla
authors.initials: AC
authors.lastname: Goldberg
authors.affiliation: Laboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil ; Laboratório de Histocompatibilidade e Imunidade Celular (LIM19), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Maria Lucia Carnevale
authors.initials: ML
authors.lastname: Marin
authors.affiliation: Departamento de Hepatologia, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Karina Rosa
authors.initials: KR
authors.lastname: Schneidwind
authors.affiliation: Divisão de Alergia e Imunologia Clínica, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Amanda Farage
authors.initials: AF
authors.lastname: Frade
authors.affiliation: Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia, 05403-000 São Paulo, SP, Brazil ; Laboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil ; Laboratório de Histocompatibilidade e Imunidade Celular (LIM19), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil ; Divisão de Alergia e Imunologia Clínica, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Departamento de Hepatologia, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Irene Kasue
authors.initials: IK
authors.lastname: Miura
authors.affiliation: Departamento de Hepatologia, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Renata Pereira Sustovich
authors.initials: RP
authors.lastname: Pugliese
authors.affiliation: Departamento de Hepatologia, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Vera Lucia Baggio
authors.initials: VL
authors.lastname: Danesi
authors.affiliation: Departamento de Hepatologia, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 05403-000 São Paulo, SP, Brazil.
authors.forename: Gilda
authors.initials: G
authors.lastname: Porta
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D019693:Hepatitis, Autoimmune / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007223:Infant; D018793:Interleukin-13 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D001323:Autoantibodies; D059811:HLA-DRB1 Chains; D018793:Interleukin-13; D007073:Immunoglobulin E