Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.


BACKGROUND Natural killer cells are involved in the complex mechanisms underlying autoimmune diseases but few studies have investigated their role in autoimmune hepatitis. Killer immunoglobulin-like receptors are key regulators of natural killer cell-mediated immune responses. METHODS AND FINDINGS KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 114 patients diagnosed with type 1 autoimmune hepatitis and compared with a group of 221 healthy controls. HLA Class I and Class II antigen frequencies were compared to those of 551 healthy unrelated families representative of the Sardinian population. In our cohort, type 1 autoimmune hepatitis was strongly associated with the HLA-B18, Cw5, DR3 haplotype. The KIR2DS1 activating KIR gene and the high affinity HLA-C2 ligands were significantly higher in patients compared to controls. Patients also had a reduced frequency of HLA-Bw4 ligands for KIR3DL1 and HLA-C1 ligands for KIR2DL3. Age at onset was significantly associated with the KIR2DS1 activating gene but not with HLA-C1 or HLA-C2 ligand groups. CONCLUSIONS The activating KIR gene KIR2DS1 resulted to have an important predictive potential for early onset of type 1 autoimmune hepatitis. Additionally, the low frequency of the KIR-ligand combinations KIR3DL1/HLA-Bw4 and KIR2DL3/HLA-C1 coupled to the high frequency of the HLA-C2 high affinity ligands for KIR2DS1 could contribute to unwanted NK cell autoreactivity in AIH-1.

DOI: 10.1371/journal.pone.0146086
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@article{Littera2016ExploringTR, title={Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.}, author={Roberto Littera and Luchino Chessa and Simona Onali and Francesco Figorilli and Sara Lai and Luca Secci and Giorgio La Nasa and Giovanni Caocci and Marcella Arras and Maurizio Melis and Sara Cappellini and Cinzia Balestrieri and Giancarlo Serra and Maria Conti and Teresa Zolfino and Michele Casale and Stefania Casu and Maria Cristina Pasetto and Lucia Barca and Claudia Salustro and Laura Matta and Rosetta Scioscia and Fausto Zamboni and Gavino Faa and Sandro Orr{\`u} and Carlo Carcassi}, journal={PloS one}, year={2016}, volume={11 1}, pages={e0146086} }