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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:...

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Autores principales: Littera, Roberto, Chessa, Luchino, Onali, Simona, Figorilli, Francesco, Lai, Sara, Secci, Luca, La Nasa, Giorgio, Caocci, Giovanni, Arras, Marcella, Melis, Maurizio, Cappellini, Sara, Balestrieri, Cinzia, Serra, Giancarlo, Conti, Maria, Zolfino, Teresa, Casale, Michele, Casu, Stefania, Pasetto, Maria Cristina, Barca, Lucia, Salustro, Claudia, Matta, Laura, Scioscia, Rosetta, Zamboni, Fausto, Faa, Gavino, Orrù, Sandro, Carcassi, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712907/
https://www.ncbi.nlm.nih.gov/pubmed/26744892
http://dx.doi.org/10.1371/journal.pone.0146086
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author Littera, Roberto
Chessa, Luchino
Onali, Simona
Figorilli, Francesco
Lai, Sara
Secci, Luca
La Nasa, Giorgio
Caocci, Giovanni
Arras, Marcella
Melis, Maurizio
Cappellini, Sara
Balestrieri, Cinzia
Serra, Giancarlo
Conti, Maria
Zolfino, Teresa
Casale, Michele
Casu, Stefania
Pasetto, Maria Cristina
Barca, Lucia
Salustro, Claudia
Matta, Laura
Scioscia, Rosetta
Zamboni, Fausto
Faa, Gavino
Orrù, Sandro
Carcassi, Carlo
author_facet Littera, Roberto
Chessa, Luchino
Onali, Simona
Figorilli, Francesco
Lai, Sara
Secci, Luca
La Nasa, Giorgio
Caocci, Giovanni
Arras, Marcella
Melis, Maurizio
Cappellini, Sara
Balestrieri, Cinzia
Serra, Giancarlo
Conti, Maria
Zolfino, Teresa
Casale, Michele
Casu, Stefania
Pasetto, Maria Cristina
Barca, Lucia
Salustro, Claudia
Matta, Laura
Scioscia, Rosetta
Zamboni, Fausto
Faa, Gavino
Orrù, Sandro
Carcassi, Carlo
author_sort Littera, Roberto
collection PubMed
description 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.
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spelling pubmed-47129072016-01-26 Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis Littera, Roberto Chessa, Luchino Onali, Simona Figorilli, Francesco Lai, Sara Secci, Luca La Nasa, Giorgio Caocci, Giovanni Arras, Marcella Melis, Maurizio Cappellini, Sara Balestrieri, Cinzia Serra, Giancarlo Conti, Maria Zolfino, Teresa Casale, Michele Casu, Stefania Pasetto, Maria Cristina Barca, Lucia Salustro, Claudia Matta, Laura Scioscia, Rosetta Zamboni, Fausto Faa, Gavino Orrù, Sandro Carcassi, Carlo PLoS One Research Article 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. Public Library of Science 2016-01-08 /pmc/articles/PMC4712907/ /pubmed/26744892 http://dx.doi.org/10.1371/journal.pone.0146086 Text en © 2016 Littera et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Littera, Roberto
Chessa, Luchino
Onali, Simona
Figorilli, Francesco
Lai, Sara
Secci, Luca
La Nasa, Giorgio
Caocci, Giovanni
Arras, Marcella
Melis, Maurizio
Cappellini, Sara
Balestrieri, Cinzia
Serra, Giancarlo
Conti, Maria
Zolfino, Teresa
Casale, Michele
Casu, Stefania
Pasetto, Maria Cristina
Barca, Lucia
Salustro, Claudia
Matta, Laura
Scioscia, Rosetta
Zamboni, Fausto
Faa, Gavino
Orrù, Sandro
Carcassi, Carlo
Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis
title Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis
title_full Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis
title_fullStr Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis
title_full_unstemmed Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis
title_short Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis
title_sort exploring the role of killer cell immunoglobulin-like receptors and their hla class i ligands in autoimmune hepatitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712907/
https://www.ncbi.nlm.nih.gov/pubmed/26744892
http://dx.doi.org/10.1371/journal.pone.0146086
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