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The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes

Genes & Immunity volume 17, pages 187–192 (2016)Cite this article

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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.

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Acknowledgements

We thank Derek Middleton for his help with the initial genotyping of the KIR genes. This work was supported by research grants from ANPCYT PICT BICENTENARIO 2010 No. 0392, PICTO-GLAXO SMITH KLINE 2011 No. 0031 and Fundación de Asistencia Social del Hospital de Clínicas.

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Authors and Affiliations

  1. Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET), Hospital de Clínicas “José de San Martín”, Universidad de Buenos Aires, Buenos Aires, Argentina

    A Podhorzer, N Paladino, G Theiler, M Capucchio, A Machicote & L Fainboim

  2. Hospital Nacional de Pediatría J. P. Garrahan, Buenos Aires, Argentina

    M L Cuarterolo & S I López

  3. Hepatopatías Infecciosas, Hospital F. J. Muñiz, Buenos Aires, Argentina

    H A Fainboim & S Paz

  4. Unidad de Cirugía Hepato-Biliar y Trasplante, Hospital Universitario Austral, Buenos Aires, Argentina

    S Montal & G Podesta

  5. Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    L Fainboim

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  1. A Podhorzer
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  2. N Paladino
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Correspondence to L Fainboim.

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Podhorzer, A., Paladino, N., Cuarterolo, M. et al. The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes. Genes Immun 17, 187–192 (2016). https://doi.org/10.1038/gene.2016.7

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  • DOI: https://doi.org/10.1038/gene.2016.7

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