Role of Gluten Intake at the Time of Hepatitis B Virus Vaccination in the Immune Response of Celiac Patients

Abstract

bSome reports have demonstrated an inadequate response to hepatitis B vaccination in patients affected by celiac disease. The aim of our study was to evaluate hepatitis B vaccination response in relation to gluten exposure status in patients with celiac disease. To measure the gluten exposure status at the time of vaccination, we considered three groups: group A (exposed to gluten), including patients vaccinated as 12-year-old adolescents (the celiac disease diagnosis was established after vaccination); group B (not exposed to gluten), including patients vaccinated as 12-year-old adolescents on a gluten-free diet at the time of vaccination; and group C (infants), including patients vaccinated at birth. The response of celiac patients to hepatitis B vaccination was compared to that of healthy subjects, i.e., those in the control group (group D). This study included 163 celiac patients (group A, 57 patients; group B, 46 patients; and group C, 60 patients) and 48 controls (group D). An inadequate response to hepatitis B immunization was present in 43.9% of patients in group A, 34.8% of patients in group B, 58.3% of patients in group C, and 8.3% of patients in group D (group A versus group D, P < 0.001; group B versus group D, P ‫؍‬ 0.002; group C versus group D, P ‫؍‬ 0.001) (no significant difference for group A versus group B and group A versus group C was evident). Our data suggest that gluten exposure does not influence the response to hepatitis B immunization and that the human leukocyte antigen probably plays the main immunological role in poor responses to hepatitis B-vaccinated celiac patients. Several studies have reported an inadequate response to hepatitis B virus (HBV) vaccination in patients affected by celiac disease (CD). Unfortunately, the causes of this impaired response are unknown (1-8).In the general population, it is recognized that several factors influence the production of protective levels of antibodies against HBV after the standard immunization. Well-known modifiers include age, obesity, smoking, drug abuse, alcoholism, infections, immune suppression, and the route of vaccination (9, 10). Additionally, hepatitis B vaccine nonresponsiveness, due to the presence of specific human leukocyte antigen (HLA) genotypes, has been described (11-13).Celiac disease (CD) is an HLA-associated immunological disease, and for this reason, a genetic predisposition as a possible cause of a lower grade of immunization to recombinant hepatitis B vaccines has been considered (4, 5). In fact, HLA-DQ2 status may predispose CD patients to fail to develop immunity after hepatitis B vaccination through a Th2 response that is inadequate for B-cell differentiation and the formation of memory B cells (5). In contrast, several studies have hypothesized gluten intake as a cause of failed immunity at the time of vaccination. Gluten might be implicated because both hepatitis B surface antigen (HBsAg) protein fragments and gliadin peptides bind to HLA-DQ2 molecules and induce proliferation of T lymphocytes. Competition bet...

Factors That Influence the Immune Response to Vaccination

“…Children with CD who are on a strict gluten-free diet have no difference in SPRs to HepB vaccination compared to those of healthy children (222,226). Apart from lower antibody responses to HepB vaccination, one study also showed that CD patients are less responsive to HepA vaccination (225).…”

Extending the Debate on Poor Response to Hepatitis B Virus Vaccination in Children With Celiac Disease: Which Question Remains?

“…However it has been supposed that gluten intake could represent the main factor in influencing a poorer response to vaccine, since in several studies, it has been observed that the percentage of responders in patients compliant with a gluten free diet (GFD) was similar to healthy subjects ( 2 , 3 ). Since type I diabetes (T1DM) and coeliac disease (CD) have the same genetic background, given by the HLA molecules that have also been identified as haplotypes associated with unresponsiveness to hepatitis B virus (HBV) vaccination (DR3 and DR4 for T1DM, DQ2 and DQ8 for CD), we firstly compared three different groups of patients, corresponding to T1DM, CD and DMT1-CD, that had in common the same HLA haplotypes, to establish the weight of specific haplotypes of HLA and/or gluten that could favor a poorer response to HBV vaccine.…”

Immune response to Hepatitis B vaccine in patients with celiac disease: A systematic review and meta-analysis

“…Therefore, we included 17 randomized clinical trials in the qualitative synthesis. [6][7][8][9][10][11][12][17][18][19][20][21][22][23][24][25][26] Three studies were further excluded because they lacked a control arm; 17-19 2 other studies, reporting both a retrospective and a prospective cohort of patients, were considered only for the retrospective design, since the prospective cohort lacked a control arm. 20,21 As a result, 14 studies were considered for the metaanalysis.…”