Response to Hepatitis B Vaccination in Patients with Celiac Disease

1 downloads 0 Views 202KB Size Report
Dec 20, 2007 - Abstract Abnormal immune response to gliadin, genetic, and environmental factors play a role in the pathogenesis of celiac disease (CD).
Dig Dis Sci (2008) 53:2156–2159 DOI 10.1007/s10620-007-0128-3

ORIGINAL PAPER

Response to Hepatitis B Vaccination in Patients with Celiac Disease Emel Ahishali Æ Gungor Boztas Æ Filiz Akyuz Æ Duygu Ibrisim Æ Sule Poturoglu Æ Binnur Pinarbasi Æ Sadakat Ozdil Æ Zeynel Mungan

Received: 21 September 2007 / Accepted: 9 November 2007 / Published online: 20 December 2007 Ó Springer Science+Business Media, LLC 2007

Abstract Abnormal immune response to gliadin, genetic, and environmental factors play a role in the pathogenesis of celiac disease (CD). Non-responsiveness to hepatitis B virus (HBV) vaccination is related to genetic features. Certain human leukocyte antigen (HLA) genotypes are more prevalent among non-responders to HBV vaccination. There is also a strong relationship between CD and these HLA genotypes. This study investigates the relationship between CD and non-responsiveness to HBV vaccination, with an emphasis on genotypic co-incidence. No statistically significant difference was noted between the ages and gender of CD patients and control subjects. Baseline serum IgA, IgM, and IgG levels of all CD patients were normal. Responsiveness to HBV vaccination was observed in 17 (68%) CD patients and all (100%) control subjects (P = 0.006). In conclusion, CD should also be sought in unresponders to HBV vaccine who are not immunosuppressed. Keywords

Celiac disease  Hepatitis B  Vaccination

Introduction Celiac disease (CD) is a genetic disease characterized by the development of immune-mediated inflammatory damage of the small intestinal mucosa precipitated by the ingestion of gluten-containing foods. Since some of the cases are asymptomatic, the true prevalence of CD is not

known. The frequency in the general population varies between 1/250–500, with the highest incidence in western European countries [1]. The female to male ratio is 2/1. Genetic, environmental, and immunological factors may play a role in the pathogenesis of the disease. The prevalence of CD in first-degree relatives is 10–15%, while this ratio reaches 70% in monozygotic twins [2]. CD is associated with certain type II human leukocyte antigens (HLA), especially with HLA-DQ2 (90–95%) and HLADQ8 (5–10%) [2, 3]. Hepatitis B virus (HBV) infection is a general health problem and one-third of the world’s population (around 2 billion people) has been infected with HBV. It is estimated that, every year, a minimum of 5,000 people die in the US from complications of HBV infection [4]. Morbidity and mortality due to hepatitis B can be reduced with vaccinations. Vaccines that have been put in practice since 1984 are efficient and safe [5–8]. In the general population, the incidence of unresponsiveness to vaccine varies between 4% and 10%. Unresponsiveness to HBV vaccine is influenced by genetic (HLA-II antigens) and non-genetic (age, gender, state of immunosuppression) factors [9]. In this study, we have evaluated the relation between CD and HBV vaccine unresponsiveness based on the knowledge that HLA-II antigens play an important role in unresponsiveness to HBV vaccine and the pathogenesis of CD.

Methods E. Ahishali (&)  G. Boztas  F. Akyuz  D. Ibrisim  S. Poturoglu  B. Pinarbasi  S. Ozdil  Z. Mungan Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390 Istanbul, Turkey e-mail: [email protected]

123

In the scope of this study, 25 patients diagnosed as CD and 20 patients as non-ulcer dyspepsia (NUD) in the Gastroenterohepatology Department of the Istanbul Faculty of Medicine, Istanbul University, Turkey, between January

Dig Dis Sci (2008) 53:2156–2159

2157

Table 1 Demographic characteristics of celiac disease (CD) patients and control subjects CD group (n = 25)

Control group (n = 20)

P-value

Female/male (%)

80/20

70/30

[0.05

Age (mean ± SD)

40.04 ± 11.65

35.85 ± 12.32

[0.05

Accompanying autoimmune disease (%)

24a



\0.001

a

Hashimoto’s thyroiditis (n = 4), Hashimoto’s thyroiditis+DM (n = 1), Grave’s disease (n = 1)

2004 and January 2005 were enrolled. The NUD patients were designated to serve as control subjects. A thorough patient history was undertaken and a physical examination was performed. With the use of upper gastrointestinal tract endoscopy, small intestinal biopsies were taken from the second part of the duodenum and evaluated according to Marsh classification. Serum IgA anti-endomysium antibodies were determined with indirect immunofluorescence assay. CD was diagnosed by positive anti-endomysium IgA in serum and histological examination. The baseline IgA, IgM, and IgG levels of CD patients were measured quantitatively by the nephelometry method (BN II, Dade Behring, Germany). NUD diagnosis was made when patients who applied with dyspeptic complaints had no biochemical, endoscopic, or pathological abnormalities to explain the symptoms. None of the CD patients and control subjects had a history of hepatitis B infection. All CD patients and control subjects were examined for HBV surface antigen (HBsAg), HBV core antibody IgG (anti-HBc IgG), and quantitative HBV surface antibody (anti-HBs). HBsAg (Sanofi Pasteur Diagnostic, France), anti-HBc IgG (BioRad, France) and anti-HBs (Behring, Germany) were measured by ELISA. All CD patients and control subjects were negative for HBsAg, anti-HBc IgG, and anti-HBs. Hepatitis B vaccine (20 lg/0.5 ml, Genhevac B, Sanofi Pasteur Diagnostic, France) was administered to all CD patients and control subjects in three doses at months 0, 1, and 6 by intramuscular injection into the deltoid muscle. Four weeks after the last dose, anti-HBs was measured quantitatively and subjects with anti-HBs [ 10 IU/ml were considered as a responder to vaccination. All statistical analyses were performed with the SPSS 11.0 program for Windows. The Mann–Whitney U-test and the chi-square test were used for statistical evaluation. A P-value \ 0.05 was considered to be statistically significant.

gender of the two groups. Among CD patients, six (24%) had an accompanying autoimmune disease (Hashimoto’s thyroiditis, Grave’s disease, and diabetes mellitus [DM]) (Table 1). Mean baseline IgA, IgM, and IgG levels of CD patients were 188.36 ± 80.02 mg/dl (normal range: 68–425 mg/ dl), 122.58 ± 50.54 mg/dl (normal range: 50–196 mg/dl), and 1,398.04 ± 469.23 mg/dl (normal range: 844– 1912 mg/dl), respectively; all of the aforementioned values were found to be within the normal ranges in CD patients. No side effect was observed in CD patients and control subjects due to HBV vaccination. According to the quantitative anti-HBs measurements after vaccination, 17 CD patients (68%) and all control subjects (100%) were found to be responders to HBV vaccination (P = 0.006) (Fig. 1). Among the six CD patients who had a coexisting autoimmune disease, two patients with Hashimoto’s thyroiditis and one patient with DM plus Hashimoto’s thyroiditis were found to be unresponders to HBV vaccination.

Discussion CD is characterized by small intestinal mucosa damage and environmental, genetic, and immunological factors may play a role in the pathogenesis of the disease. CD can occur together with a number of endocrinologic, neurologic, 100% 90% 80% 70% 60% 50% 40% 30%

Results

20% 10%

The mean age of the 25 CD patients (20 women, five men) and the 20 control subjects (14 women, six men) were 40.04 ± 11.65 and 35.85 ± 12.32 years, respectively. There was no significant difference between the age and

0% CD patients

Control subjects

Fig. 1 Responsiveness to hepatitis B vaccination in CD patients and control subjects

123

2158

hepatologic, rheumatologic, cardiologic, and dermatologic diseases. The frequency of comorbidity with autoimmune disorders is estimated to be 10 times higher when compared to the normal population. The most common of these autoimmune diseases are Type 1 DM and autoimmune thyroid disease [2, 10]. In our study, 24% of CD patients had an autoimmune disease, but no incidence of autoimmune disease was noted in the control subjects. Vaccination is an efficient and secure way of protection from common HBV infections [7, 8, 11]. It is known that age, smoking, obesity, and the male gender predispose to a low rate of responsiveness to HBV vaccination [8]. In a meta-analysis by Fisman et al. [12], it is shown that an increased risk of unresponsiveness to HBV vaccination was found among older individuals, even when older individuals were defined as being as young as 30 years. In a study on non-smoking and non-obese healthy volunteers older than 40 years, the response rate to HBV vaccination was observed to be lower than the general population and the rate was elevated with an additional dose of vaccination [13]. In our study, the majority of the patients were female and there was no significant difference of gender distribution between CD patients and control subjects. The mean age of our study group comprising CD patients and control subjects was below 40 years (38.18 ± 12.00 years), with the CD patients not statistically significantly older than the control subjects. The two groups were similar in terms of age and gender, however, unresponsiveness to HBV vaccination displayed a significant difference, and 32% of CD patients and none of the control subjects were found to be unresponders to HBV vaccine. In unresponsiveness to HBV vaccination, genetic specifications are important. A decade ago, it was shown that HBV vaccine response is related to a ‘‘major histocompatibility complex’’ (MHC) [14, 15]. Today, it is known that HLA-II antigens play a role in unresponsiveness to HBV vaccination [16–19]. In a study by Ho¨hler et al. [18], it was shown that complement C4 played an additional role in the response to HBV vaccine, and a number of genes and environmental factors are also important. In the present study, we have found that half of the patients who had autoimmune disease along with CD were unresponders to HBV vaccine. Therefore, the existence of an accompanying autoimmune disease seems to aggravate the state of unresponsiveness to HBV in CD, which emphasizes the involvement of genetic factors in the pathogenesis. In our study, the response rate of CD patients to HBV vaccination was found to be 68%. This rate is too low when compared to the general population (90–95%). Among the NUD patients whom we designated as control subjects, the response rate to HBV vaccination was 100%. In a study by Noh et al. [9], the response rate to HBV vaccination in CD patients was found to be 32%. In that study, hepatitis B

123

Dig Dis Sci (2008) 53:2156–2159

response testing and HLA typing was performed in 15 patients and it was found that the response rate was lower in homozygotes for HLA-B8, DR3, and DQ2. The authors suggested that this high rate of HBV vaccine responsiveness in CD was related to genetic features. CD is associated with HLA-II, especially with HLA-DQ2 and HLA-DQ8, and it is known that HLA-II antigens play a role in the unresponsiveness to HBV vaccine. In our study, we could not perform HLA genotype analysis, which constitutes a main drawback, and, therefore, we could not present data focusing on genetic aspects. We believe that future studies are needed to be performed on a larger number of patients and using HLA typing tests. In conclusion, CD may show a serious clinical presentation with malabsorption or, as seen in many patients, it may show minimal symptoms or atypical findings. For this reason, CD should also be sought in unresponders to HBV vaccine who are not immunosuppressed.

References 1. Murray JA (1999) The widening spectrum of celiac disease. Am J Clin Nutr 69:354–365 2. Bai J, Zeballos E, Fried M, Corazza GR, Schuppan D, Farthing MJG, Catassi C, Greco L, Cohen H, Krabshuis JH (2005) WGOOMGE practice guideline. Celiac disease. World Gastroenterol News 10:6–12 3. Rodrigo L (2006) Celiac disease. World J Gastroenterol 12:6585– 6593 4. Keeffe EB, Dieterich DT, Han SB, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright T (2004) A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. Clin Gastroenterol Hepatol 2:87–106 5. McAleer WJ, Buynak EB, Maigetter RZ, Wampler DE, Miller VJ, Hilleman MR (1984) Human hepatitis B vaccine from recombinant yeast. Nature 307:178–180 6. Scolnick EM, McLean AA, West DJ, McAleer WJ, Miller VJ, Buynak EB (1984) Clinical evaluation in healthy adults of a hepatitis B vaccine made by recombinant DNA. JAMA 251:2812–2815 7. Kao JH, Chen DS (2002) Global control of hepatitis B virus infection. Lancet Infect Dis 2:395–403 8. Bonanni P, Bonaccorsi G (2001) Vaccination against hepatitis B in health care workers. Vaccine 19:2389–2394 9. Noh KW, Poland GA, Murray JA (2003) Hepatitis B vaccine nonresponse and celiac disease. Am J Gastroenterol 98:2289– 2292 10. Farrell RJ, Kelly CP (2002) Celiac sprue and refractory sprue. In: Feldman M, Friedman LS, Sleisenger MH (eds) Sleisenger & Fordtran’s gastrointestinal and liver disease, 7th edn. WB Saunders, Philadelphia, Pennsylvania, pp 1817–1837 11. Lemon SM, Thomas DL (1997) Vaccines to prevent viral hepatitis. N Engl J Med 336:196–204 12. Fisman DN, Agrawal D, Leder K (2002) The effect of age on immunologic response to recombinant hepatitis B vaccine: a meta-analysis. Clin Infect Dis 35:1368–1375 13. Das K, Gupta RK, Kumar V, Kar P (2003) Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders. World J Gastroenterol 9:1132–1134

Dig Dis Sci (2008) 53:2156–2159 14. Kruskall MS, Alper CA, Awdeh Z, Yunis EJ, Marcus-Bagley D (1992) The immune response to hepatitis B vaccine in humans: inheritance patterns in families. J Exp Med 175:495–502 15. Alper CA, Kruskall MS, Marcus-Bagley D, Craven DE, Katz AJ, Brink SJ, Dienstag JL, Awdeh Z, Yunis EJ (1989) Genetic prediction of nonresponse to hepatitis B vaccine. N Engl J Med 321:708–712 16. Schuenke KW, Cook RG, Rich RR (1998) Binding specificity of a class II-restricted hepatitis B epitope by DR molecules from responder and nonresponder vaccine recipients. Hum Immunol 59:783–793 17. Ho¨hler T, Meyer CU, Notghi A, Stradmann-Bellinghausen B, Schneider PM, Starke R, Zepp F, Sa¨nger R, Clemens R, Meyer

2159 zum Bu¨schenfelde KH, Rittner C (1998) The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg. Hum Immunol 59:212–218 18. Ho¨hler T, Stradmann-Bellinghausen B, Starke R, Sa¨nger R, Victor A, Rittner C, Schneider PM (2002) C4A deficiency and nonresponse to hepatitis B vaccination. J Hepatol 37:387–392 19. Wang C, Tang J, Song W, Lobashevsky E, Wilson CM, Kaslow RA (2004) HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination. Hepatology 39:978–988

123