title: Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Regional Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Littera
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.|Department of Internal Medicine, University Hospital, Cagliari, Italy.
authors.forename: Luchino
authors.initials: L
authors.lastname: Chessa
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Onali
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Figorilli
authors.affiliation: Medical Genetics, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Lai
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Secci
authors.affiliation: Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.|Hematology Unit, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Nasa
authors.affiliation: Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.|Hematology Unit, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caocci
authors.affiliation: Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Arras
authors.affiliation: Regional Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Melis
authors.affiliation: Departmental Unit of Liver Transplantation, G. Brotzu Hospital, Cagliari, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cappellini
authors.affiliation: Department of Internal Medicine, University Hospital, Cagliari, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Balestrieri
authors.affiliation: Department of Internal Medicine, University Hospital, Cagliari, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Serra
authors.affiliation: Department of Internal Medicine, University Hospital, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Conti
authors.affiliation: Departmental Unit of Liver Transplantation, G. Brotzu Hospital, Cagliari, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Zolfino
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Casale
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Casu
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pasetto
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Barca
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Salustro
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Matta
authors.affiliation: Center for the Study of Liver Diseases, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Rosetta
authors.initials: R
authors.lastname: Scioscia
authors.affiliation: Department of General Surgery, Division of liver and pancreas transplantation, G. Brotzu Hospital, Cagliari, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Zamboni
authors.affiliation: Department of Surgical Science, Division of Pathology, University of Cagliari, Cagliari, Italy.
authors.forename: Gavino
authors.initials: G
authors.lastname: Faa
authors.affiliation: Medical Genetics, R. Binaghi Hospital, ASL 8, Cagliari, Italy.|Medical Genetics, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Orrù
authors.affiliation: Medical Genetics, R. Binaghi Hospital, ASL 8, Cagliari, Italy.|Medical Genetics, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Carcassi
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D059911:HLA-B18 Antigen / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D019693:Hepatitis, Autoimmune / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D054344:Receptors, KIR2DL3 / Q000235:genetics / Q000276:immunology; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000276:immunology
chemical_list: D015415:Biomarkers; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; C037505:HLA-C*05 antigen; D015803:HLA-DR3 Antigen; C515078:KIR2DL3 protein, human; C496212:KIR2DS1 protein, human; C515083:KIR3DL1 protein, human; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1