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

• Published in: Genes and immunity Vol. 17; no. 3; pp. 187 - 192
• Main Authors: Podhorzer, A, Paladino, N, Cuarterolo, M L, Fainboim, H A, Paz, S, Theiler, G, Capucchio, M, López, S I, Machicote, A, Montal, S, Podesta, G, Fainboim, L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2016; Nature Publishing Group
• Subjects: 13/31; 45/77; 631/208/205; 631/208/248/144; 631/250/38; Adult; Alleles; Antigens; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Cell receptors; Chronic active hepatitis; Development and progression; Drb1 protein; Female; Gene Expression; Genes; Genetic aspects; Genetic research; Haplotypes; Health aspects; Hepatitis; Hepatitis, Autoimmune - diagnosis; Hepatitis, Autoimmune - genetics; Hepatocytes; Histocompatibility antigen HLA; Histocompatibility antigens; HLA Antigens - genetics; HLA histocompatibility antigens; Human Genetics; Humans; Immunoglobulin-like receptors; Immunoglobulins; Immunology; Killer cell immunoglobulin-like receptors; Killer cells; KIR protein; KIR2DL2 gene; Lymphocytes T; Male; Membrane proteins; original-article; Pediatrics; Polymorphism, Genetic; Potassium channels (inwardly-rectifying); Properties; Receptors, KIR - genetics; Risk factors; White people; Argentina
• ISSN: 1466-4879; 1476-5470; 1476-5470
• DOI: 10.1038/gene.2016.7

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.