title: Th-17 cells infiltrate the liver in human biliary atresia and are related to surgical outcome.
abstract: BACKGROUND
  Biliary atresia (BA), a cholangiopathy of unknown etiology is associated with intrahepatic mononuclear cell infiltrate. An abnormal reaction to viral exposure has been hypothesized in some cases. We aimed to investigate the nature of the CD4+ hepatic infiltrate in defined clinical variants of BA by quantification of inflammatory cell components.
  
  
  METHODS
  Liver biopsies of infants obtained at Kasai portoenterostomy (KPE) were stained immunohistochemically using monoclonal antibodies to Tbet, GATA-3, FOXP3 and interleukin (IL) 17, identifying Th-1, Th-2, Tregs and Th-17 cells respectively. T cells were counted with the aid of a graticule. Data are reported as median (range) of cells per high-power-field (×400) and compared using nonparametric statistical tests with P≤0.05 regarded as significant.
  
  
  RESULTS
  Liver biopsies from BA (n=37) and age-matched cholestatic controls (e.g. alpha-1-anti trypsin deficiency, Alagilles syndrome, n=12) were investigated. BA infants were divided into three groups: cytomegalovirus IgM +ve (CMV; n=9); BA splenic malformation (BASM; n=9) and isolated BA (IBA; n=19). All T-cell subsets were present in the portal tracts, with an overrepresentation of Th-1 (P<0.001) and Th-17 (P<0.03), but not Th-2 (P=0.94) or Tregs (P=0.15), compared to controls. Th-1 cells predominated in the CMV group; (18 [7-37] vs. 3 [0-14] [BASM] and vs. 5 [3-23] [IBA]; P<0.01 both), while no subgroup differences were seen for Th-17 cells. The degree of Th-1 cell infiltrate inversely correlated with platelet count (rS=-0.49; P<0.01). Th-17 cells were fewer (6 [2-11] vs. 11 [8-20]; P=0.02) in infants who cleared their jaundice (n=15, <20μmol/L) although this did not translate to improved native liver survival (P=0.17).
  
  
  CONCLUSIONS
  Th-17 cells infiltrate the liver in BA and are associated with a worse surgical outcome; a Th-1 profile predominates in CMV-associated BA.
authors.affiliation: Department of Paediatric Surgery, King's College Hospital, London SE5 9RS, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Hill
authors.affiliation: Institute of Liver Studies, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital, London SE5 9RS, UK.
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.affiliation: Institute of Liver Studies, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital, London SE5 9RS, UK.
authors.forename: Munther
authors.initials: M
authors.lastname: Hussain
authors.affiliation: Paediatric Liver, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital, London SE5 9RS, UK.
authors.forename: Nedim
authors.initials: N
authors.lastname: Hadzic
authors.affiliation: Paediatric Liver, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital, London SE5 9RS, UK.
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.affiliation: Institute of Liver Studies, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital, London SE5 9RS, UK.
authors.forename: Diego
authors.initials: D
authors.lastname: Vergani
authors.affiliation: Department of Paediatric Surgery, King's College Hospital, London SE5 9RS, UK. Electronic address: Markdav2@ntlworld.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Davenport
mesh_terms: D001656:Biliary Atresia / Q000276:immunology* / Q000601:surgery / Q000821:virology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000276:immunology* / Q000601:surgery / Q000821:virology; D011171:Portoenterostomy, Hepatic; D058504:Th17 Cells / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: Biliary atresia; Inflammatory response; Interleukin-17; T-cells; Tregs