Celiac disease (CD) is an immune-mediated inflammatory enteropathy triggered by gluten exposure in genetically susceptible individuals and it has a high prevalence approaching 1% of the US population. Our knowledge of CD pathogenesis has recently made rapid progress. The disorder is now considered the result of a complex interplay of genetic and environmental factors that explain the wide spectrum of clinical manifestations ranging from asymptomatic to severe malabsorption. Although gliadin and related cereal proteins are the undisputed triggers of CD, the presence of IgA is considered essential in the pathogenesis of CD. Hence specific IgAs are applied in diagnostic as serological markers of CD. As an advanced company in the field of therapeutic molecular development, Creative Biolabs established mature IgA research platforms and we are glad to share our experience about CD and IgA with our partners over the world.
Clinical Presentation of Celiac Disease
The clinical presentation of CD varies greatly and ranges from asymptomatic to severe malnutrition. The most common manifestations of CD include abdominal pain, increased frequency of bowel movements, weight loss, bone disease, anemia, and weakness. However, in the atypical form of the disease, gastrointestinal symptoms may be absent or less pronounced, while extraintestinal features are more prominent such as anemia, osteoporosis, short stature, infertility, and neurologic problems. In serological tests, IgA anti-tissue transglutaminase (TTG) antibody is the favored test for screening for CD with sensitivities ranging from 93 to 95%and specificities approaching 96%.
Fig.1 Manifestations of celiac disease. (Domsa, 2020)
IgA and Celiac Disease
Exposure of the upper small bowel mucosa to gluten in susceptible people causes an increase of intestinal permeability, then an immune-mediated reaction that involves the innate and the adaptive immune responses might take place. The main autoantigen of CD is the enzyme tissue transglutaminase (tTG) which is found in the lamina propria of the small bowel and deamidates glutamine residues in gluten to form glutamic acid. Glutamic acid was recognized by the antigen-presenting cells that express the HLA-DQ2/DQ8 receptors for T lymphocytes, furthermore, the gluten-specific T cell response leads to the release of specific IgA and IgG as well as immunomodulators such as cytokines and interferons, which induces crypt hyperplasia and villous blunting secondary to intestinal epithelial cell death induced by intraepithelial lymphocytes as classical symptoms of CD.
Fig.2 Pathogenesis of celiac disease. (Alaedini, 2005)
Treatment of Celiac Disease
For the diagnosis of celiac disease, serological tests indicate the presence of IgA tTG and IgA endomysium antibodies (EMA). In patients with normal IgA levels, IgA tTG testing has 95% sensitivity and specificity.
The only efficient treatment of CD involves life-long dietary elimination of gluten which is found in wheat, barley, and rye. However, a strict GFD is often difficult to achieve due to inconspicuous sources of gluten. Glucocorticoids can induce symptomatic improvement but are not recommended for use in uncomplicated CD due to long-term side effects and relapse of symptoms upon discontinuation. Moreover, there are also new therapies under study: oral enzyme supplements, larazotide acetate, irreversible transglutaminase inhibitor, HLA-DQ2 blocking treatment, and vaccines.
Although there is no standardized treatment regimen for CD at present, specific IgA as biomarkers provides an approach to diagnosis as early as possible to prevent the complications. If you are interested in the research of CD, or for more details in the research of the therapeutic molecular field, please feel free to contact us.
References
- Domsa, E. M.; et al. Celiac disease: a multi-faceted medical condition. J Physiol Pharmacol. 2020, 71(1), 3-4.
- Antiga, A.; et al. Narrative review: celiac disease: understanding a complex autoimmune disorder. Annals of internal medicine. 2005, 142(4), 289-298.
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