title: HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease.
abstract: OBJECTIVE
  Celiac disease (CD) is a T-lymphocyte-mediated small intestinal enteropathy triggered and maintained by dietary gluten, with a strong genetic component mapping to the HLA genes encoding for the class II DQ(alpha1*0501, beta1*02) molecule. Damage of the small intestine may cause a variety of clinical signs ranging from isolated long-standing iron-deficiency anemia refractory to iron supplementation to forms of severe malnutrition that may become life threatening. However, patients carrying the typical intestinal lesions of CD and presenting no symptoms at all (silent CD) are also a common clinical observation. Since it is commonly assumed that clinical signs and symptoms tend to correlate with the severity of the intestinal damage, the purpose of this study was to investigate whether particular HLA class II genotypes might also influence the extent of intestinal damage and consequently the clinical presentation of the disease.
  
  
  METHODS
  We retrospectively compared histological grading of celiac disease intestinal biopsies with HLA haplotype, age at onset of disease and clinical signs and symptoms.
  
  
  RESULTS
  Our findings showed that homozygosis for the DQB1*0201 allele is associated with a higher severity of the histological score (p<0.008). Of note for the clinician, this work also suggests that the same type 3c of intestinal damage causes a different clinical syndrome, depending on the patient's age.
  
  
  CONCLUSIONS
  The genetic predisposition at the HLA-DQB1 locus influences the severity of the mucosal damage in a dose-dependent manner, but not the clinical presentation, of celiac disease.
authors.affiliation: Department of Biological Science and Biotechnology, University of Cagliari, Cagliari, Italy. rdjores@yahoo.com
authors.forename: Rita-Désirée
authors.initials: RD
authors.lastname: Jores
authors.forename: Fulvia
authors.initials: F
authors.lastname: Frau
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
authors.forename: Maria
authors.initials: M
authors.lastname: Grazia Clemente
authors.forename: Sandra
authors.initials: S
authors.lastname: Orrù
authors.forename: Marco
authors.initials: M
authors.lastname: Rais
authors.forename: Stefano
authors.initials: S
authors.lastname: De Virgiliis
authors.forename: Mauro
authors.initials: M
authors.lastname: Congia
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000032:analysis; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen