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Published online June 2, 2008
PEDIATRICS Vol. 121 No. 6 June 2008, pp. e1570-e1576 (doi:10.1542/peds.2007-2446)
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Hepatitis B
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ARTICLE

Gluten Intake Interferes With the Humoral Immune Response to Recombinant Hepatitis B Vaccine in Patients With Celiac Disease

Éva Nemes, MDa, Éva Lefler, MDb, László Szegedi, MDc, Anikó Kapitány, MScd, Judit B. Kovács, MD, PhDe, Márta Balogh, MDf, Katalin Szabados, MDg, Judit Tumpek, MDd, Sándor Sipka, MD, PhDd, Ilma R. Korponay-Szabó, MD, PhDe,h

a Department of Pediatrics
d Third Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
b Laboratory of National Public Health and Medical Services, Debrecen, Hungary
c Department of Internal Medicine, Kenézy Gyula County Hospital, Debrecen, Hungary
e Department of Gastroenterology-Nephrology, Heim Pál Children's Hospital, Budapest, Hungary
f Department of Pediatrics, Markusovszky Hospital, Szombathely, Hungary
g Department of Infectology, Hetényi Géza County Hospital, Szolnok, Hungary
h Pediatric Research Center, University of Tampere Medical School, Tampere, Finland

OBJECTIVE. Patients with celiac disease, who often carry human leukocyte antigen-DR3;DQ2, are prone to inadequate response to hepatitis B immunization. We evaluated vaccine response in relation to disease activity and whether previous treatment with a gluten-free diet influences the achievement of protective antibody titers.

PATIENTS AND METHODS. We studied 128 children and adolescents with celiac disease and 113 age-matched control subjects. Twenty-two patients with celiac disease were prospectively immunized after diagnosis during dietary treatment (group 1). A total of 106 (group 2) and the control subjects received vaccination by mass immunization in schools at 14 years of age regardless of diet status and when celiac disease was still undiagnosed in 27 of these children. Diet compliance and celiac disease activity were monitored by measurement of antibodies against transglutaminase and endomysium. Vaccine response was determined by measuring antihepatitis B antibodies from serum.

RESULTS. The seroconversion after hepatitis B vaccination was 95.5% in group 1. All of these patients carried human leukocyte antigen DQ2. The response rate in group 2 was 50.9% and correlated with gluten intake (untreated patients: 25.9%, non-strict diet: 44.4%, strict diet: 61.4%). Treated and compliant patients did not significantly differ from control subjects (75.2%). Thirty-seven antihepatitis B–negative patients with celiac disease received a booster during a controlled gluten-free diet, and 36 (97.3%) seroconverted, irrespective of the presence of human leukocyte antigen DQ2.

CONCLUSIONS. Nonresponse to recombinant hepatitis B surface antigen may be a sign of undiagnosed celiac disease. However, there is a good vaccine response in adequately treated patients. Human leukocyte antigen DQ alleles do not seem to have a primary role. Revaccination is recommended during a controlled gluten-free diet.

Key Words: celiac disease • gluten-free diet • hepatitis B immunization • vaccine nonresponse • endomysium antibody • transglutaminase antibody • disease activity

Abbreviations: HBV—hepatitis B virus • HBsAg—hepatitis B surface antigen • HLA—human leukocyte antigen • CD—celiac disease • TG2—type 2 transglutaminase • anti-HBs—antihepatitis B surface antibody • HBe—hepatitis B envelope • Ig—immunoglobulin • EMA—endomysium antibody • CI—confidence interval

Accepted Nov 14, 2007.


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