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Celiac disease (CD) is a multifactorial autoimmune inflammatory disease of the small intestine that is triggered in genetically susceptible persons by the ingestion of gluten, found in wheat, rye, and barley, and other related plant proteins (prolamins). The condition is thought to result from the activation of both a T-cell and B-cell immune response, leading to mucosal inflammation, villous atrophy, and crypt hyperplasia, and is self-perpetuating with continued exposure to gluten. The enzyme tissue transglutaminase (tTGA) is now known to be the target autoantigen of the abnormal autoimmune response.
Celiac Disease Complications Are Serious
The classical presentation of CD, with gluten-induced abnormal intestinal mucosa and intestinal malabsorption, is considered to be the “tip” of the iceberg—that is, it is considered to be far less common than silent disease and other presentations. Atypical clinical manifestations include dermatitis herpetiformis, insulin-dependent diabetes mellitus, autoimmune thyroid disease, and chronic fatigue. Untreated CD is associated with multiple important short- and long-term complications, including nutritional derangements, anemia, reduced bone density, and malignancies such as intestinal T-cell lymphoma. Early diagnosis and strict adherence to a gluten-free diet are thought to reduce the risk of complications.
Celiac Disease Statistics: Increasing Prevalence
The true prevalence of CD has recently been assessed using sensitive and specific serological tests that can detect patients with few or no symptoms. Screening studies have confirmed that it is one of the most common lifelong disorders among European and American Caucasians, with a prevalence in the general population that is close to 1%. With the exception of Asia and some areas of Africa where CD prevalence is lower or higher, the prevalence of CD in other regions is similar to that seen in Europe and North America. A 2009 study that tested sera collected in the mid-twentieth century from approximately 9000 healthy adults, and recent sera from approximately 12,000 sex-matched subjects, found that the prevalence of undiagnosed celiac disease has markedly increased from 0.2% to between 0.8% and 0.9%. In addition, all-cause mortality in the older cohort was almost fourfold greater in individuals with undiagnosed celiac disease than in those who were seronegative.1 This study tested for tTGA and endomysial IgA antibodies (IgA-tTGA and IgA-EMA, respectively).
Celiac Disease Tests
The new serologic tests have altered the classic diagnostic pathway of CD in adults, which was based on clinical suspicion and duodenal biopsy. The 2006 medical position statement published by the American Gastroenterological Association2 concluded that high-risk symptomatic individuals (those with symptoms that could be the result of celiac disease) should undergo serological testing for IgA-tTGA. The sensitivity and specificity of tests for IgA-tTG are both greater than 90%. The tests for IgA-EMA are similarly sensitive and specific; however, the assay is more time-consuming and subjective, and for the primary care setting, the single most efficient test for the detection of CD is the IgA-tTGA.2 In cases of IgA deficiency, which is uncommon, testing for IgG-EMA or IgG-tTGA is recommended.2 Positive serology plus distal duodenal biopsies (multiple specimens) is the gold standard for the diagnosis of CD, according to the 2007 Practice Guidelines of the World Gastroenterology Organization.3 When the results of biopsy and serology are equivocal, HLA testing for the CD-associated DQ alleles can be used to exclude the diagnosis of CD.
Screening and Monitoring Celiac Disease
Who should be screened for CD remains controversial. Although it has been established that life-threatening complications may develop in the absence of treatment, the Practice Guidelines of the World Gastroenterology Organization concluded that there was not enough evidence to carry out general screening.3 The authors of the study discovering the increased prevalence and mortality of CD have also concluded that more research is needed.1
Antibody testing can be used to monitor patients with CD who are following a gluten-free diet for response to treatment. In addition, it is reasonable to perform serological testing for patients with nonceliac gluten sensitivity who have symptoms of diarrhea, gas, and bloating, to rule out CD.4
- Gold Standard Diagnostics (Davis, CA) offers the CE-marked and FDA-approved Fidis™ Celiac IgA kit for the simultaneous detection of human IgA antibodies directed against gliadin or tTGA. This test is manufactured by Theradiag (Marne La Vallee, France), and is based on the use of color-coded microspheres covalently coupled to antigen, and a benchtop flow cytometer interfaced to digital signal processing hardware and software (Luminex® xMAP® technology). The test is performed in a 96-well microplate with a filtering membrane.
- Scimedx Corporation (Denville, NJ) offers the FDA-approved Anti-Human (Umana) Eu-tTG IgA Assay, which is a 96-well ELISA (12 strips with 8 microwells coated with human recombinant tTGA antigen) for the semiquantitative detection of IgA-specific antibodies directed against tTGA in human serum.
- Immco Diagnostics, Inc. (Buffalo, NY) has a national reference laboratory that provides testing for celiac disease, and also offers CE-marked enzyme immunoassays (EIAs) for celiac disease. The ImmuLisa™ Celiac tTG rHuman Tissue Transglutaminase Antibody ELISA is a 96-well solid-phase immunoassay for the qualitative and semiquantitative detection of IgA-tTGA.
References
- Rubio-Tapia, A.; Kyle, R.A. et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology 2009, 137, 88–93.
- Rostom, A.; Murray, J. et al. Medical Position Statement on Celiac Disease. Gastroenterology 2006, 131, 1977–80.
- http://www.worldgastroenterology.org/assets/downloads/en/pdf/guidelines/04_celiac_disease.pdf.
- Medscape Gastroenterology, Mar 2013. Going gluten-free: value beyond celiac disease? David A. Johnson, M.D.