Auteur Topic: Autoimmunity: Does celiac disease trigger autoimmune thyroiditis?  (gelezen 6387 keer)


  • Gold Member
  • *****
  • Berichten: 1152
Omdat ik niet weet of dit artikel volledig op de site blijft staan heb ik hieronder de gehele tekst geplaatst (Engelstalig) van een artikel in

Nature Reviews Endocrinology 5, 190-191 (April 2009) | doi:10.1038/nrendo.2009.46

"Researchers have now revealed a possible immunopathologic link between the two diseases..."
" is celiac disease related to autoimmune thyroiditis"

Autoimmune thyroiditis has increased prevalence in patients with celiac disease and vice versa.
New research suggests that serum transglutaminase 2 autoantibodies, which are present in patients with celiac disease, might have a role in the development of thyroid dysfunction.

Celiac disease is a chronic, autoimmune, inflammatory disorder of the small intestine that affects 1% of the population.
In celiac disease, an interplay of genetic and environmental factors causes an inappropriate immune response to wheat gluten and the similar proteins of barley and rye.1

The disease is characterized by small-bowel mucosal inflammation, villous atrophy and malabsorption.
Typical symptoms include diarrhea, weight loss and fatigue. In many patients, however, extraintestinal symptoms dominate, while many others are asymptomatic.

Celiac disease is associated with a number of autoimmune conditions, including autoimmune thyroiditis.2, 3, 4
Research has found that a gluten-free diet results in symptomatic improvement for patients with either celiac disease or autoimmune thyroiditis. Researchers have now revealed a possible immunopathologic link between the two diseases that involves transglutaminase 2 autoantibodies.

Transglutaminase 2 (also known as tissue transglutaminase) is considered essential to the development of celiac disease.
This ubiquitous enzyme catalyzes the post-translational modification of proteins, including the deamidation of gluten peptides.

In patients with celiac disease, modification of gluten peptides by transglutaminase 2 triggers an immune response and inflammation.
This inappropriate immune response is thought to occur because individuals who are genetically susceptible to celiac disease express specific haplotypes of cell surface receptors of antigen-presenting cells that preferentially bind to the deamidated gluten peptides.5 In addition, a concomitant type 2 T-helper-cell response results in the production of autoantibodies against transglutaminase 2.

The inflammatory process in patients with celiac disease is thought to cause oxidative stress and activation of transglutaminase 2 in many tissues.

When IgA autoantibodies against transglutaminase 2 bind to this enzyme in organs such as the liver, heart and brain, they can contribute to the extraintestinal conditions associated with celiac disease.5
In their study, Naiyer et al.6 provide evidence that IgA autoantibodies against transglutaminase 2, which are present in the sera of patients with active celiac disease, also react with transglutaminase 2 in thyroid tissue and thereby contribute to the development of thyroid disease.

The study demonstrates that the binding of IgA autoantibodies against transglutaminase 2 to this enzyme occurs in follicular epithelial cells (Figure 1) as well as extracellularly, in the interfollicular space.

To assess the importance of this binding of transglutaminase 2 autoantibodies to thyroid tissue, the researchers assessed thyroid autoimmunity in patients with celiac disease.

Frequency of thyroid-autoantibody positivity was increased in the sera of patients who had active celiac disease, compared with that in sera of healthy individuals or patients with Crohn disease.

Moreover, a positive correlation was found to exist between titers of autoantibodies against tranglutaminase 2 and those against thyroperoxidase, which suggests a relationship between celiac disease and presence of the autoantibodies found in autoimmune thyroid disease.

Figure 1
IgA autoantibodies against transglutaminase 2 present in the sera of patients with active celiac disease bind to this enzyme in thyroid tissue.

Link>> High resolution image and legend (10 KB)
Figures and tables index
Download Power Point slide (61 KB)
a |

A primate thyroid tissue section that shows epithelial cells stained red by cytokeratin ( 60 magnification). b |
The same thyroid tissue section incubated with serum from a patient with active celiac disease.
Binding of IgA autoantibodies against transglutaminase 2 to this enzyme in the epithelial cells is shown by the pattern of green fluorescence (fluorescein isothiocyanate green;  60 magnification). Image courtesy of A. J. Naiyer, G. Bhagat & P. H. Green, Celiac Disease Center, Columbia University College of Physicians and Surgeons, USA.

Further results from Naiyer et al. revealed that extended duration of gluten exposure in patients with celiac disease seemed to be a predisposing factor for autoimmune thyroiditis.
In addition, age at diagnosis of celiac disease is an independent predictor of autoimmune disease and, therefore, early diagnosis and treatment might prevent the development of such conditions.

One positive aspect is the development of new serum antibody assays, such as the transglutaminase 2 autoantibody and the IgA endomysial antibody, which have considerably improved detection of the disease; however, small-intestine biopsy still remains the 'gold standard' for diagnosis of celiac disease.7

Several questions nevertheless remain, the most pertinent of which is how is celiac disease related to autoimmune thyroiditis?
We must bear in mind that genetic, immune and environmental factors are likely to be involved and, therefore, any pathologic mechanism is probably extremely complex.
Researchers have proposed a number of possible mechanisms, but only further research can clarify the situation.5, 8 Intriguingly, one potential mechanism might involve the hygiene hypothesis.

The hygiene hypothesis proposes that a lack of early childhood exposure to infections—owing to the improvement in standards of hygiene in the past couple of decades—results in a predisposition to certain immune disorders.
Findings from a Finnish group suggest that celiac disease is one such disorder.

To study the effect of socioeconomic status on the prevalence of celiac disease, the Finnish researchers included two distinct populations that share similar ancestry, but live in very different socioeconomic conditions—those of Russian Karelia and Finland.9

The lower prevalence of autoantibodies against transglutaminase 2 and celiac disease in Russian Karelia than Finland was linked to the lower socioeconomic environment in the Russian region.
Another arm of this study assessed the effect of socioeconomic environment on the development of thyroid autoimmunity.
Again, a lower prevalence of autoimmunity, independent of ethnic background, was found in the Russian area compared to that in Finland.10
Socioeconomic conditions, therefore, might affect an individual's susceptibility to celiac disease and associated autoimmune conditions, such as autoimmune thyroiditis.

The findings by Naiyer et al. strengthen evidence of a close association between celiac disease and autoimmune thyroiditis, and hint that autoantibodies against transglutaminase 2 (probably together with factors such as cellular immunity and the environment) contribute to the development of autoimmune thyroiditis.
This evidence should prompt diagnostic testing for autoimmune thyroiditis, or even subclinical hypothyroidism, in patients with celiac disease.

Practice point
Celiac disease is associated with autoimmune thyroiditis
Clinicians should screen for autoimmune thyroiditis in all patients with celiac disease
Early diagnosis and treatment of celiac disease seems to prevent the manifestation of autoimmune thyroiditis

Slide 1:
Slide 2:


Groeten, Ine