title: Contribution of histological, serological, and genetic factors to the clinical heterogeneity of adult-onset coeliac disease.
abstract: OBJECTIVE
  Although the factors predisposing to coeliac disease (CD) are largely understood, it remains unclear what determines the clinical heterogeneity of the disease. The aim of this study was to explore the contribution of histological, serological, and genetic factors to disease presentation.
  
  
  METHODS
  The study was designed as a retrospective chart review of 384 unrelated Caucasian patients diagnosed with CD after the age of 16 at a single UK centre.
  
  
  RESULTS
  We found that 8.8% of IgA-competent CD patients were endomysial antibody (EMA)-negative. Compared with the EMA-positive group, EMA-negative CD patients had a lower prevalence of iron deficiency (52.0% versus 72.6%, p=0.03) and Marsh IIIb-c lesions (66.7% versus 85.3%, p=0.03). Histological severity at diagnosis correlated with anaemia (p<0.01), folate deficiency (p<0.01), and iron deficiency (p=0.05), but no other laboratory or clinical features. Compared with human leucocyte antigen (HLA)-DQ2.5-positive patients, those carrying HLA-DQ2.2 were similar in terms of all the characteristics we considered, whereas those carrying HLA-DQ8 had a lower frequency of EMA positivity (62.5% versus 92.6%, p<0.01). The proportion of EMA-positive patients increased with frequency of the HLA-DQB1*0201 allele (76.7% versus 92.3% versus 96.4% for 0 versus 1 versus 2 alleles, p<0.01); no other evidence of a gene-dose effect of HLA-DQB1*0201 was observed.
  
  
  CONCLUSIONS
  Histological severity at diagnosis of CD is associated with anaemia and some micronutrient deficiencies, but no other clinical features. The proportion of EMA-positive patients is higher amongst those carrying HLA-DQ2 than in those carrying HLA-DQ8, and is highest in HLA-DQ2 homozygotes. We found no correlation between frequency of the HLA-DQ alleles encoding HLA-DQ2.5 and CD severity.
authors: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. harry.thomas@doctors.org.uk
authors: Harry J
authors: HJ
authors: Thomas
authors: Tariq
authors: T
authors: Ahmad
authors: Chandima
authors: C
authors: Rajaguru
authors: Martin
authors: M
authors: Barnardo
authors: Bryan F
authors: BF
authors: Warren
authors: Derek P
authors: DP
authors: Jewell
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000740:Anemia / Q000453:epidemiology; D001323:Autoantibodies / Q000097:blood; D002446:Celiac Disease / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012189:Retrospective Studies; D012720:Severity of Illness Index; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens