Hepatitis B vaccine nonresponse and celiac disease

Am J Gastroenterol. 2003 Oct;98(10):2289-92. doi: 10.1111/j.1572-0241.2003.07701.x.


Objectives: There is a genetic predisposition to hepatitis B vaccine nonresponse. The link between human leukocyte antigen (HLA) genotype and ineffective development of immunity to the hepatitis B vaccine has been characterized in multiple studies. Celiac disease has a strong association with a particular HLA genotype of DQ2; interestingly, this HLA genotype is seen in association with nonresponders to the hepatitis B vaccine. We report a disproportionate number of patients with celiac disease who are nonresponders to the hepatitis B vaccine series.

Methods: We reviewed the hepatitis B vaccine records, serological tests for anti-hepatitis B surface antigen antibody (anti-HBs), and HLA genotypes of celiac disease patients identified as nonresponders to hepatitis B vaccine. Subjects were identified from a database of patients diagnosed with celiac disease at our institution or referred to our center for evaluation and management of celiac disease between November, 2000, and October, 2002.

Results: A total of 23 subjects were reviewed. All had a clinical and pathological diagnosis of celiac disease. All subjects reported receiving the full series of hepatitis B vaccinations. Of the subjects, 19 had testing for hepatitis B vaccine response. Of these 19 subjects, 13 did not achieve long-term immunity as seen by the negative qualitative or quantitative anti-HBs antibody titer. All tested subjects were either homozygous or heterozygous for DQ2.

Conclusions: We postulate that celiac disease patients may have a significant predisposition to hepatitis B vaccine nonresponse. Both celiac disease and hepatitis B vaccine nonresponse is genetically mediated. Celiac disease patients may have a failure of induction of humoral immune response needed for development of long term immunity; the mechanism for this is unclear.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Celiac Disease / diagnosis*
  • Celiac Disease / epidemiology
  • Celiac Disease / genetics
  • Female
  • Follow-Up Studies
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Hepatitis B / epidemiology
  • Hepatitis B / immunology*
  • Hepatitis B / prevention & control
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / immunology
  • Humans
  • Immunity / physiology*
  • Incidence
  • Male
  • Middle Aged
  • Phenotype
  • Retrospective Studies
  • Risk Assessment
  • Sampling Studies


  • HLA Antigens
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines