Nancy A. Melville

May 21, 2015

LEIPZIG, Germany — In children with celiac disease, immunologic response to the hepatitis B vaccine is impaired, and neither a gluten-free diet nor boosters appear to improve that, according to new research presented here at the 33rd Annual Meeting of the European Society for Paediatric Infectious Diseases.

"This response should be evaluated at diagnosis," said Maria José Pérez, MD, from Henares Hospital in Coslada, Spain.

Although previous studies have shown this reduced response, most have been limited by low numbers of patients with celiac disease and even lower numbers of control patients, Dr. Pérez explained.

Gluten has been implicated in the impaired response, and two studies have shown a response to the hepatitis B vaccine similar to that in the general population after patients switch to a gluten-free diet.

In their study, Dr. Pérez and her colleagues assessed the immune response to the vaccine in children with celiac disease. The team evaluated 214 children with celiac disease and 346 control patients who had completed the hepatitis B vaccine regimen in the first year of life. All patients were vaccinated before gluten was introduced into their diets.

Antibody titers were measured for each child to determine response to the vaccine. Nonresponse was defined as a level of hepatitis B surface antibody below 10 mUI/mL.

Overall, nonresponse was higher in children with celiac disease than in control subjects (68.7% vs 60.7%). For children younger than 5 years, this difference was significant (50.0% vs 30.1%; P = .015).

Table. Children With Undetectable Hepatitis B Surface Antibody

Age Group Celiac Group, % Control Group, % P Value
<5 years 9.7 1.2 .018
5 to <10 years 20.0 6.8 .04
0 to <10 years 14.0 8.4 .034


In children with celiac disease, the researchers found no relation between level of antibody and time since the last intake of gluten.

"Gluten intake has no role in the genesis of suboptimal immunologic response to hepatitis B vaccine in patients with celiac disease," Dr. Pérez reported.

Over time, levels of antibody decreased in both groups. "When evaluating serologic response to hepatitis B vaccine, time elapsed since vaccination should be considered," she said.

In another study, Dr. Pérez and a different team of researchers looked at the role of human leukocyte antigen genes in vaccine response. Previous studies have identified these genes as the main marker for lack of response to the hepatitis B vaccine, so the team looked at the association in children with celiac disease.

The study involved 188 children with celiac disease and 204 healthy control subjects.

The rate of responders to the vaccine was significantly lower in children with the human leukocyte antigen DR3 gene than in those without (22.41% vs 47.56%; P < .001). And the rate of undetectable levels of antibody was higher in children with the human leukocyte antigen DQ2 gene than in those without (13.96% vs 3.91%; P = .002).

"DQ2 and DR3 expression is associated with an impaired immunologic response to hepatitis B vaccine," Dr. Pérez reported.

In another study by another team led by Dr. Pérez, researchers assessed the effectiveness of a booster vaccine.

Hep B Booster

The prospective study involved 72 children with celiac disease who were vaccinated in the first year of life and whose antibody levels were below 10 mUI/mL.

The researchers found no change in levels after the children received a single booster.

"A single booster dose of hepatits B vaccine is not effective in achieving an adequate immune response," especially in children with undetectable levels of antibody, the researchers report.

Children with celiac disease and undetectable levels of antibody should be revaccinated with the complete immunization regimen, they advise.

But antibodies alone might not tell the whole story in terms of response to the vaccine, said Joseph Murray, MD, from the Mayo Clinic in Rochester, Minnesota.

"Protection from hepatitis B is likely not dependent on antibodies alone," he told Medscape Medical News. "It also involves T-cell response, so the lack of measurable antibodies is not absolute proof of no protection."

However, the findings support previous research on the poor response to vaccine in children with celiac disease, said Dr. Murray, who is coauthor of a recent report on celiac disease (Clin Gastroenterol Hepatol. Published online July 19, 2014).

"The data are generally consistent with previous data on the genetic association between DQ2 genetics and poor response to hep B vaccine," he said.

Dr. Murray said he considers such evidence when managing his patients of all ages.

"I routinely test for hepatitis B response in vaccinated celiac patients, especially if they are younger or work in exposure-risk settings, such as healthcare or corrections," he said.

"If they don't have a response to a single booster, I recommend they redo the vaccine after 1 year of a gluten-free diet, based on previous studies that suggest active disease impairs response."

The researchers report no relevant financial relationships. Dr. Murray is editor of the book, Mayo Clinic Going Gluten Free.

33rd Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID): Abstracts 463 and 464 and poster MPW06. Presented May 15, 2015.


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