title: The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes.
abstract: We have previously reported a strong association between HLA-DRB1*1301 and type 1 pediatric autoimmune hepatitis (PAH) and between HLA-DR*0405 and adult autoimmune hepatitis (AAH). Because human killer cell immunoglobulin-like receptors are known to be associated with susceptibility to autoimmune diseases, we investigated the frequencies of HLA-A, B, C, DRB1 and KIR genes in 144 type 1 PAH and 86 AAH patients, which were compared with 273 healthy controls. We demonstrated in PAH the increased frequency of the functional form of KIR2DS4-Full Length (KIR2DS4-FL), which in combination with HLA-DRB1*1301 revealed a strong synergistic effect (odds ratio=36.5). PAH-KIR2DS4-FL+ subjects have shown an increased frequency of their putative HLA-C*02, 04 and 06 ligands. KIR analysis of PAH also revealed a decreased frequency of KIR2DL2 gene and its ligand. In contrast, AAH cases have shown a weaker increased frequency of KIR2DS4-FL, a lack of synergistic effect with HLA class II antigens and a moderate association with HLA-DRB1*0405. Of note, we demonstrated that liver T cells have a unique pattern of KIR expression. These results show a KIR gene involved in autoimmune hepatitis and suggest a stronger genetic influence for the early onset type I autoimmune hepatitis.
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Podhorzer
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Paladino
authors.affiliation: Hospital Nacional de Pediatría J. P. Garrahan, Buenos Aires, Argentina.
authors.forename: M L
authors.initials: ML
authors.lastname: Cuarterolo
authors.affiliation: Hepatopatías Infecciosas, Hospital F. J. Muñiz, Buenos Aires, Argentina.
authors.forename: H A
authors.initials: HA
authors.lastname: Fainboim
authors.affiliation: Hepatopatías Infecciosas, Hospital F. J. Muñiz, Buenos Aires, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Paz
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Theiler
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Capucchio
authors.affiliation: Hospital Nacional de Pediatría J. P. Garrahan, Buenos Aires, Argentina.
authors.forename: S I
authors.initials: SI
authors.lastname: López
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Machicote
authors.affiliation: Unidad de Cirugía Hepato-Biliar y Trasplante, Hospital Universitario Austral, Buenos Aires, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Montal
authors.affiliation: Unidad de Cirugía Hepato-Biliar y Trasplante, Hospital Universitario Austral, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Podesta
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.|Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Fainboim
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D019693:Hepatitis, Autoimmune / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D006680:HLA Antigens; C473953:KIR2DS4 protein, human; D054340:Receptors, KIR