title: Human leucocyte antigens and pediatric autoimmune liver disease: diagnosis and prognosis.
abstract: An association of human leukocyte antigen (HLA) class II alleles with autoimmune conditions is increasingly being used for diagnostic purposes. The aim of our study was to examine whether HLA class II alleles in pediatric-onset autoimmune liver disease (pAILD) may serve as diagnostic markers and if they correlate with clinical outcome parameters. HLA-DRB1 alleles of 76 children with pAILD (autoimmune hepatitis [AIH], autoimmune sclerosing cholangitis [AISC], primary sclerosing cholangitis [PSC]) and of 50 healthy blood donors as control group were analyzed retrospectively. Diagnosis of these patients was confirmed by the autoimmune hepatitis score including liver histology, which has been re-evaluated by a blinded liver pathologist, and by bile duct imaging, as appropriate. Our results showed significant association of HLA-DRB1*03 with AIH1 and AISC with 82 % specificity for AIH. For pAILD (excluding AIH2), HLA-DRB1*03 homozygosity had specificity of 98 %, whereas sensitivity is low. Remission in HLA-DRB1*03-positive patients appears to be less likely. HLA-DRB1*13 is significantly associated with PSC and also with AIH1.
  
  
  CONCLUSIONS
  HLA-DRB1 alleles provide supportive information for diagnostic workup in patients with liver disease, but they were not suitable for differentiation within pAILD. Their prognostic value could be helpful but needs to be evaluated further.
  
  
  BACKGROUND
  • HLA-DRB1*03 is NOT associated with pediatric AIH in a previous national study. • In other studies, HLA-DRB1*03 is associated with AIH1. • HLA-DRB1*13 is associated with PSC. • HLA-DRB1*04 is described as protective for AILD. What is New: • HLA-DRB1 four-digit typing for all alleles and for all subgroups of pAILD combined with re-assessment of liver histology • HLA-DRB1*03:01 is associated with pediatric AIH1 and AISC. • HLA-DRB1*03:01 appears to be a prognostic marker. • HLA-DRB1*13:01 is associated with pediatric AIH1 in mixed ethnicity cohort. • HLA-DRB1*04 does not show any protective effect for pAILD.
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany. Junge.Norman@mh-hannover.de.
authors.forename: Norman
authors.initials: N
authors.lastname: Junge
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Tiedau
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Murielle
authors.initials: M
authors.lastname: Verboom
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallensleben
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
authors.affiliation: Institute for Pathology, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Jerome
authors.initials: J
authors.lastname: Schlue
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Imeke
authors.initials: I
authors.lastname: Goldschmidt
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Eva-Doreen
authors.initials: ED
authors.lastname: Pfister
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl- Neuberg-Str 1, 30625, Hannover, Niedersachsen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D015209:Cholangitis, Sclerosing / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D059811:HLA-DRB1 Chains
keywords: Autoimmune hepatitis; Autoimmune sclerosing cholangitis; HLA-DRB1; Human leukocyte antigens; Liver; Liver transplantation; Pediatric autoimmune liver disease; Primary sclerosing cholangitis