title: KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection.
abstract: Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain HLA-KIR combinations have been found to protect against viral infections. In this study, we analysed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P<.001) and HC (10%) (crude OR, 12.38; P<.001). Similar results were obtained for the HLA-C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P<.10) and HC (60%) (crude OR, 3.56; P<.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR, 0.10; P<.05). These results suggest a detrimental role of HLA-A-Bw4 and HLA-C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%) and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection.
authors.affiliation: Dipartimento dell'Emergenza e dei Trapianti d'Organo, Università di Bari Aldo Moro, Bari, Italy.
authors.forename: D
authors.identifier: 0000-0002-9728-3806
authors.initials: D
authors.lastname: Di Bona
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Aiello
authors.affiliation: Dipartimento di Scienze per la Promozione della Salute e Materno-Infantile "G. D'Alessandro", Università di Palermo, Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Colomba
authors.affiliation: Dipartmento Jonico in Sistemi Giuridici ed Economici del Mediterraneo: Società, Ambiente, Culture, Università di Bari Aldo Moro, Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bilancia
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Accardi
authors.affiliation: Dipartimento di Scienze per la Promozione della Salute e Materno-Infantile "G. D'Alessandro", Università di Palermo, Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rubino
authors.affiliation: Dipartimento BioMedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Giannitrapani
authors.affiliation: Dipartimento BioMedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tuttolomondo
authors.affiliation: Dipartimento di Scienze per la Promozione della Salute e Materno-Infantile "G. D'Alessandro", Università di Palermo, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cascio
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università di Foggia, Foggia, Italy.
authors.forename: M F
authors.initials: MF
authors.lastname: Caiaffa
authors.affiliation: Unità Operativa di Medicina Trasfusionale, AOUP, Palermo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: Dipartimento BioMedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.|Unità Operativa di Medicina Trasfusionale, AOUP, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Candore
authors.affiliation: Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Duro
authors.affiliation: Dipartimento dell'Emergenza e dei Trapianti d'Organo, Università di Bari Aldo Moro, Bari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Macchia
authors.affiliation: Dipartimento BioMedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Montalto
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.|Unità Operativa di Medicina Trasfusionale, AOUP, Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Caruso
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.|Unità Operativa di Medicina Trasfusionale, AOUP, Palermo, Italy.
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054344:Receptors, KIR2DL3 / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D054344:Receptors, KIR2DL3
keywords: 
  HLA
  ; 
  killer cell immunoglobulin-like receptor
  ; 
  natural killer
  ; hepatitis B virus