title: Coeliac disease screening in first-degree relatives on the basis of biopsy and genetic risk.
abstract: BACKGROUND
  Serological markers of coeliac disease (CD) lack diagnostic value to identify mild histopathological lesions mainly in adults at risk of CD.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the usefulness of human leukocyte antigen (HLA)-DQ2/8 genotyping, followed by duodenal biopsy for the detection of CD in adult first-degree relatives (FDRs) of patients with CD.
  
  
  METHODS
  Ninety-two adult DQ2/8 positive FDRs were consecutively included. A duodenal biopsy was offered irrespective of the serology result or associated symptoms. The clinical features, associated autoimmune diseases and biochemical parameters were recorded.
  
  
  RESULTS
  Sixty-seven FDRs (mean age 34 years) underwent a duodenal biopsy. Histopathological alterations were found in 32 (48%) and showed the following stages: 12 Marsh I (18%), one Marsh II (1.5%), four Marsh IIIA (6%), five Marsh IIIB (7.5%) and 10 Marsh IIIC (15%). Positive serological markers were present in 17/67 (25%), with only one showing Marsh I and the remainder presenting some degree of duodenal atrophy (Marsh III). In addition, 33/67 (54%) had gastrointestinal symptoms, with dyspepsia being the most prevalent. The distribution of symptoms, anaemia and autoimmune disease was independent of the duodenal histopathological stage. Serology-based screening would diagnose 50% of the cases showing any degree of CD spectrum and miss 6% of the cases with mucosal atrophy.
  
  
  CONCLUSIONS
  Adult FDRs of patients with CD can benefit from a screening strategy on the basis of HLA-DQ genotyping, followed by a duodenal biopsy. Gastrointestinal symptoms and lymphocytic enteritis are common findings that may benefit from a gluten-free diet.
authors.affiliation: aGastroenterology Unit bPathology Department cPaediatric Department, University Hospital of León, Altos de Nava s/n dInstitute of Molecular Biology (INBIOMIC) eMicrobiology Department fInstitute of Biomedicine (IBIOMED), University of León, León, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Vaquero
authors.forename: Alberto
authors.initials: A
authors.lastname: Caminero
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nuñez
authors.forename: Mercedes
authors.initials: M
authors.lastname: Hernando
authors.forename: Cristina
authors.initials: C
authors.lastname: Iglesias
authors.forename: Javier
authors.initials: J
authors.lastname: Casqueiro
authors.forename: Santiago
authors.initials: S
authors.lastname: Vivas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002446:Celiac Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D004386:Duodenum / Q000473:pathology; D004415:Dyspepsia / Q000209:etiology; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012720:Severity of Illness Index; D011503:Transglutaminases / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins