Autoimmune thyroid disease (AITD), one of the most common autoimmune diseases, had several pathogenesis, including both genetic and environmental factors and is one of risk factor for thyroid dysfunction [1,2]. One of potential environmental causes are infectious agents such as Helicobacter pylori, which may cause chronic inflammation and autoimmune reactivity in susceptible subjects [3,4]. Although some studies support a role for H. pylori in AITD, this remains controversial [5-14].

H. pylori infection was prevalent in Asian populations in the last 10 years. Though the prevalence of H. pylori infection and annual reinfection rate found to be decreased especially below the age of 40’s after introduction of triple therapy, H. pylori infection is still prevalent in Korean population [15]. The incidence of H. pylori infection in the Korean population above 16 years of age was 59.6% in 2005 [15]. Furthermore, extra-gastric diseases, especially autoimmune diseases that might be related to H. pylori infection have received attention recently [16,17]. However, data regarding the relationship between H. pylori infection and thyroid autoimmunity are limited in Asian populations, in which H. pylori infection is extremely prevalent.

In the present study we investigated the association between H. pylori infection and AITD in the Korean population. Our findings indicated that thyroid autoimmunity is significantly associated with H. pylori infection.

A total of 5,967 subjects without past or family histories of thyroid disease were included. Of these, 465 subjects with equivocal results for H. pylori IgG antibody were excluded. Finally 5,502 subjects (female 42.8%) were analysed. The mean age was 51.9 years. H. pylori infection was found in 2,875 subjects (52.3%), and thyroid autoimmunity was present in 430 (7.8%).

The clinical characteristics of the subjects according to H. pylori infection and thyroid autoimmunity are summarized in Tables 1 and 2, respectively. Subjects with H. pylori infection were older than those without H. pylori infection (p < 0.01), and there were significant differences between the age quartiles in the frequency of H. pylori infection. The proportions of individuals positive for H. pylori Ab were 46.1%, 56.1%, 52.0%, and 53.5%, in Q1, Q2, Q3, and Q4, respectively (p < 0.01) (Table 1). On the other hand, the proportion of females was significantly higher in the TPO-Ab positive group than in the TPO-Ab negative group (64.2% vs. 41.0%, p < 0.01) (Table 2).

We compared thyroid autoimmunity according to H. pylori infection. Prevalence of TPO-Ab positivity was higher in subjects with H. pylori infection (246 out of 2,875 subjects [8.6%] vs. 184 out of 2,627 subjects [7.0%], p = 0.03) (Fig. 1). We performed a multivariate analysis to adjust for the possible interaction between thyroid autoimmunity and various clinical parameters. The serologic results of H. pylori were significantly related to TPO-Ab positivity after adjusting for age, sex, and body mass index (odds ratio, 1.02; 95% confidence interval, 1.00 to 1.03; p = 0.04).

Infectious agents have been implicated in the pathogenesis of autoimmunity [20]. Epidemiological and serological surveys have suggested the possibility of a link between Yersina enterocolitica infection and Graves disease, a link which might be explained by molecular mimicry [21,22]. Infectious agents may lead to thyroid autoimmunity by a variety of mechanisms, such as inducing modification of self-antigens, mimicry of self-molecules, activation of polyclonal T cells, alteration of the idiotype network, formation of immune complexes, and induction of major histocompatibility complex molecules on thyroid epithelial cells [4]. A homologous 11-residue peptide in both gastric parietal cell antigen and thyroid peroxidase suggests the existence of an epitope common to both of the two antigens [23]. There may be cross reaction between antibodies produced during H. pylori infection and thyroid antigens, leading to development of AITD. Interestingly, elevated chemokine response to H. pylori have been observed in AITD patients [24].

H. pylori is a spiral-shaped, flagellated, gram-negative bacterium, and colonizes the stomach of about 50% of the world’s population [16]. It can cause dyspepsia, acute and chronic gastritis, peptic ulceration, mucosa associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In particular, the most virulent strain of H. pylori was identified by the presence of cytotoxin-associated gene A (CagA), and individuals infected with the CagA-positive strain of H. pylori have an increased risk of peptic ulcer and gastric cancer [25]. Furthermore, several studies have reported a significant correlation between CagA-positive strains and AITD. Because our study was based on data from health check-ups, CagA status was not investigated.

Previous studies regarding the association between H. pylori and AITD have generally been from Italy, Czechoslovakia, and Iran, in which H. pylori infections are prevalent. In Korea, the seroprevalence of H. pylori infection was 59.6% in 2005 and decreased to 54.4% in 2011, according to Lim et al. [26]. It is unclear whether the prevalence of H. pylori infection and a decreasing trend of H. pylori seroprevalence will affect the association between H. pylori and AITD.

Our study had several limitations. First, we defined H. pylori infection based on a serologic test, which detects both past and current infections. Second, our definition of AITD did not differentiate between Graves disease and Hashimoto thyroiditis. Third, we did not test for the presence of CagA because our study was based on health check-up data. Finally, there might be concern about false positive results in H. pylori IgG test and TPO-Ab assay. However, H. pylori IgG test is highly specific and had no cross-reactivity to Campylobacter coli microorganism. We also excluded patients with equivocal results to avoid a concern of false positive results. TPO-Ab assay has cross-reactivity with human anti-Tg antibodies and human Tg. However, anti-Tg antibody could one of other representative of thyroid autoimmunity and we excluded subjects with history of thyroid disease. Therefore, there might be little concern about false positive results.

In conclusion, our findings suggest that H. pylori infection may be associated with AITD. Further studies are needed to confirm the role of H. pylori infection in AITD.