title: Influence of HLA class I, HLA class II and KIRs on vertical transmission and chronicity of hepatitis C virus in children.
abstract: OBJECTIVE
  There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT), but this does not explain all cases. We study the role of the immunogenetic profile (HLA, KIRs and KIR-ligand binding) of mothers and children in HCV-MTCT and in chronicity in the children.
  
  
  METHODS
  79 HCV-RNA (+) mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16. HLA-class-I and II and KIRs were determined by Luminex.
  
  
  RESULTS
  MTCT study: The presence of HLA-C1-ligand in mothers and/or their children reduces the risk of transmission (mothers: Pc = 0.011, children: P = 0.033), whereas the presence of HLA-C2C2-ligand in mothers increases it (Pc = 0.011). In children KIR2DL3-HLA-C1 is a protector factor (Pc = 0.011). Chronicity in children study: Maternal DQA1*01 allele (Pc = 0.027), KIR2DS1 (Pc = 0.011) or KIR3DS1 (Pc = 0.011) favours chronicity in the child. The presence of the DQB1*03 allele (Pc = 0.027) and KIR2DS3 (P = 0.056) in the child and homozygosity for KIR3DL1/3DL1 (Pc = 0.011) and for the HLA-Bw4/Bw4 ligand (P = 0.027) is associated with viral clearance, whereas the presence of HLA-Bw6 ligand (P = 0.027), the binding of KIR3DS1-HLA-Bw4 (P = 0.037) and heterozygosity for KIR3DL1/3DS1 (Pc = 0.011) favour viral chronicity. Mother/child allele matching: In the joint HLA analysis, matching was greater between mothers and children with chronic infection vs those who had cleared the virus (67%±4.1 vs 57%±1.2, P = 0.003).
  
  
  CONCLUSIONS
  The HLA-C1 ligand in the mother is related to MTCT, while several genetic factors of the mother or child are involved in the chronification or clearance of infection in the child. Matching allelic data is considered to be an indicator of HCV chronicity in the child and can be used as a potential prognostic test. This implies that NK cells may play a previously undocumented role in protecting against MTCT and that both NK cell immunity and adaptive T-cell responses may influence viral clearance in infected children.
authors.affiliation: Paediatric Unit, San Cecilio University Hospital and Virgen de las Nieves University Hospital, Granada, Spain.|Paediatric Department, Granada University, Granada, Spain.|CIBER for Liver and Digestive Disease (CIBERehd), Instituto de Salud Carlos III, Spain.|Instituto de Investigación Biosanitaria de Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Extremera
authors.affiliation: Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: E J
authors.initials: EJ
authors.lastname: Pavón-Castillero
authors.affiliation: Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Florido
authors.affiliation: CIBER for Liver and Digestive Disease (CIBERehd), Instituto de Salud Carlos III, Spain.|Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Muñoz de Rueda
authors.affiliation: Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Muñoz-Gámez
authors.affiliation: Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Casado
authors.affiliation: Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Carazo
authors.affiliation: CIBER for Liver and Digestive Disease (CIBERehd), Instituto de Salud Carlos III, Spain.|Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Quiles
authors.affiliation: Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.|Medicine Department, Granada University, Granada, Spain.
authors.forename: S M
authors.initials: SM
authors.lastname: Jiménez-Ruiz
authors.affiliation: CIBER for Liver and Digestive Disease (CIBERehd), Instituto de Salud Carlos III, Spain.|Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gila
authors.affiliation: Instituto de Investigación Biosanitaria de Granada, Spain.|Biostatistic Department, Granada University, Granada, Spain.
authors.forename: J D
authors.initials: JD
authors.lastname: Luna
authors.affiliation: CIBER for Liver and Digestive Disease (CIBERehd), Instituto de Salud Carlos III, Spain.|Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: León
authors.affiliation: CIBER for Liver and Digestive Disease (CIBERehd), Instituto de Salud Carlos III, Spain.|Instituto de Investigación Biosanitaria de Granada, Spain.|Clinical Management Unit of Digestive Diseases, Research Unit, San Cecilio University Hospital, Granada, Spain.|Medicine Department, Granada University, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Salmerón
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006526:Hepatitis C / Q000635:transmission* / Q000821:virology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D011446:Prospective Studies; D054340:Receptors, KIR / Q000235:genetics*; D019562:Viral Load
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR