Serological markers and HLA genes among healthy first-degree relatives of patients with coeliac disease

Lancet. 1991 Nov 30;338(8779):1350-3. doi: 10.1016/0140-6736(91)92234-s.


Coeliac disease may remain undiagnosed because of the non-specific nature of the presenting symptoms. Several antibody tests are claimed as markers for this condition but a direct comparison of the available tests has not been reported. The probands and healthy first-degree relatives of 42 families with coeliac disease were studied. Histological examination of biopsy specimens revealed jejunal mucosal villous atrophy compatible with coeliac disease in 13 of 122 relatives. Reticulin-antibody-positive relatives with or without jejunal mucosal atrophy were genetically similar to the probands of the families (DR3 gene frequencies 55.3%-60.0%). Gliadin-antibody-positive relatives with normal mucosa were genetically different from the probands (DR3 gene frequency 16.7% versus 55.3%). IgA reticulin and endomysium antibodies detected 92.3% of subjects with silent coeliac disease. The only case that was missed had selective IgA deficiency and was positive for IgG-class reticulin antibodies. By contrast, gliadin antibodies detected only half of the cases. Follow-up of the 7 reticulin-antibody-positive relatives with normal mucosa revealed 2 further cases of coeliac disease and 1 of dermatitis herpetiformis during the next three years. Our family study shows that healthy reticulin-antibody-positive first-degree relatives of coeliac disease patients, irrespective of the state of the jejunal mucosa, are genetically similar to known coeliac disease patients. Reticulin-antibody positivity is an indicator of both silent and latent coeliac disease.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / blood*
  • Biomarkers
  • Celiac Disease / genetics*
  • Celiac Disease / immunology*
  • Celiac Disease / pathology
  • Female
  • Gliadin / immunology
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Haplotypes
  • Humans
  • Jejunum / pathology
  • Male
  • Reticulin / immunology


  • Antibodies
  • Biomarkers
  • HLA Antigens
  • Reticulin
  • Gliadin