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Celiac Disease (CD)

Celiac disease (CD) is a chronic autoimmune mediated disorder triggered by gliadin, a protein found in wheat, rye, and barley. CD is an unique autoimmune disease in that its key genetic elements (human leukocyte antigen (HLA)-DQ2 and HLA-DQ8), the auto-antigen involved (tissue transglutaminase (tTG)), and the environmental trigger (gluten) are all well-defined. CD is one of the most common autoimmune disorders, with a reported prevalence of 0.5–1% of the general population. The disease can occur at any age from early childhood to the elderly, with two peaks of onset – one shortly after weaning with gluten in the first 2 years of life, and the other in the second or third decades of life. 

The gold standard for CD diagnosis is the combination of mucosal changes detected by duodenal biopsy and by positivity of serological tests. 

Diagnosis and Challenges

  • The diagnosis of CD can be challenging since symptoms can vary significantly from patient to patient. Extraintestinal symptoms are common in both children and adults. They include iron deficiency microcytic anemia,  and osteopenia or osteoporosis. Growth retardation and short stature can raise the suspect of an underlying CD. Other signs can include tooth enamel defects, aphthous stomatitis hypertransaminasemia, headache, paresthesia, neuroinflammation, anxiety and depression. The clinical presentation may also include changes in reproductive function characterized by late menarche, amenorrhea, recurrent miscarriages, premature birth, early menopause, and changes in the number and mobility of spermatozoa. 

Gold Standard Laboratory Testing

  • The gold standard for CD diagnosis is represented by the combination of mucosal changes detected by duodenal biopsy and by positivity of serological tests (anti-tTG antibodies, anti-endomysium antibodies (EmA), and deamidated gliadin peptide (DGP) antibodies).  Anti-Endomysial Antibody (EmA) is an antibody against the smooth muscle’s inter-myofibrillar substance. The assay has a sensitivity and specificity of over 95% Anti-Tissues Transglutaminase Antibody is a calcium-dependent enzyme, which catalyzes the covalent bond and cross-linking of proteins irreversibly. Autoantigen against TG2 causes  the deamidation of the bond between glutamine and lysine, present in gluten.  IgA anti-TG2 Ab is the most widely used test both for the diagnosis and initial screening for CD because of its very high sensitivity and specificity, ease of use, and its quantitative capability.  Immunoglobulin A (IgA) tTG levels also correlate with the degree of severity of mucosal damage, and a titer of 10 folds or higher over the upper limit of normal (ULN) predicts presence of villous abnormality with very high specificity. 

  • Anti-deamidated gliadin peptides Ab (DGP) is directed against deamidated gliadin peptides and is another serologic marker for the diagnosis of CD. Initially, IgA DGP was reported to be equally sensitive and specific as IgA tTG Ab. A recent systematic review and meta-analysis reported the pooled sensitivity of anti-DGP Ab to be 87.8% (95% CI, 85.6–89.9%), and of specificity 94.1% (95% CI, 92.5–95.5%). Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide

Celiac Disease (CD) Tests

Selected References

  1. Caio, G., Volta, U., Sapone, A., Leffler, D. A., De Giorgio, R., Catassi, C., & Fasano, A. (2019). Celiac disease: a comprehensive current review. BMC medicine, 17(1), 1-20.

  2. Fasano, A., & Catassi, C. (2012). Celiac disease. New England Journal of Medicine, 367(25), 2419-2426.

  3. Werkstetter, K. J., Korponay-Szabó, I. R., Popp, A., Villanacci, V., Salemme, M., Heilig, G., ... & Sadat, A. T. E. (2017). Accuracy in diagnosis of celiac disease without biopsies in clinical practice. Gastroenterology, 153(4), 924-935.

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