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Celiac disease (gluten-sensitive enteropathy, celiac sprue) results from an immune-mediated inflammatory process that occurs in genetically susceptible individuals following ingestion of wheat, rye, or barley proteins.(1) The inflammation in celiac disease occurs primarily in the mucosa of the small intestine, which leads to villous atrophy.(1) Common clinical manifestations related to gastrointestinal inflammation include abdominal pain, malabsorption, diarrhea, and/or constipation.(2) Clinical symptoms of celiac disease are not restricted to the gastrointestinal tract. Other common manifestations of celiac disease include failure to grow (delayed puberty and short stature), iron deficiency, recurrent fetal loss, osteoporosis, chronic fatigue, recurrent aphthous stomatitis (canker sores), dental enamel hypoplasia, and dermatitis herpetiformis.(3) Patients with celiac disease may also present with neuropsychiatric manifestations including ataxia and peripheral neuropathy, and are at increased risk for development of non-Hodgkin lymphoma.(1,2) The disease is also associated with other clinical disorders including thyroiditis, type I diabetes mellitus, Down syndrome, and IgA deficiency.(1,3)
Celiac disease tends to occur in families; individuals with family members who have celiac disease are at increased risk of developing the disease. Genetic susceptibility is related to specific HLA markers. More than 97% of individuals with celiac disease in the United States have DQ2 and/or DQ8 HLA markers, compared to approximately 40% of the general population.(3)
A definitive diagnosis of celiac disease requires a jejunal biopsy demonstrating villous atrophy.(1-3) Given the invasive nature and cost of the biopsy, serologic tests may be used to identify individuals with a high probability of having celiac disease. Because no single laboratory test can be relied upon completely to establish a diagnosis of celiac disease, those individuals with positive laboratory results should be referred for small intestinal biopsy, thereby decreasing the number of unnecessary invasive procedures. Celiac disease is associated with a variety of autoantibodies, including endomysial, tissue transglutaminase (tTG), and deamidated gliadin antibodies.(4) Although the IgA isotype of these antibodies usually predominates in celiac disease, individuals may also produce IgG isotypes, particularly if the individual is IgA deficient.(2) The most sensitive and specific serologic tests are tTG and deamidated gliadin antibodies.
Testing for IgA and IgG antibodies to unmodified gliadin proteins is no longer recommended because of the low sensitivity and specificity of these tests for celiac disease; however, recent studies have identified specific B-cell epitopes on the gliadin molecule that, when deamidated by the enzyme tissue transglutaminase, have increased sensitivity and specificity for celiac disease.(5,6) The tests for deamidated gliadin antibodies, IgA and IgG, replace the older gliadin antibody tests, which have been discontinued at Mayo Clinic. The sensitivity and specificity of test DGLDN / Gliadin (Deamidated) Antibodies Evaluation, IgG and IgA, Serum for untreated, biopsy-proven celiac disease were comparable to TSTGP / Tissue Transglutaminase (tTG) Antibodies, IgA and IgG Profile, Serum in a recent study conducted at Mayo Clinic.(5)
The treatment for celiac disease is maintenance of a gluten-free diet.(1-3) In most patients who adhere to this diet, levels of associated autoantibodies decline and villous atrophy improves. This is typically accompanied by an improvement in clinical symptoms. For evaluation purposes, all serologic tests ordered for the diagnosis of celiac disease should be performed while the patient is on a gluten-containing diet. Once a patient has initiated the gluten-free diet, serologic testing may be repeated to assess the response to treatment. In some patients, it may take up to 1 year for antibody titers to normalize. Persistently elevated results suggest poor adherence to the gluten-free diet or the possibility of refractory celiac disease.(1)
See Celiac Disease Diagnostic Testing Algorithm in Special Instructions for the recommended approach to a patient suspected of celiac disease.
An algorithm is available for monitoring the patient's response to treatment, see Celiac Disease Routine Treatment Monitoring Algorithm in Special Instructions.
For your convenience, we recommend utilizing cascade testing for celiac disease. Cascade testing ensures that testing proceeds in an algorithmic fashion. The following cascades are available; select the appropriate one for your specific patient situation.
Algorithms for the cascade tests are available in Special Instructions.
-CDCOM / Celiac Disease Comprehensive Cascade: complete testing including HLA DQ
-CDSP / Celiac Disease Serology Cascade: complete testing excluding HLA DQ
-CDGF / Celiac Disease Gluten-Free Cascade: for patients already adhering to a gluten-free diet
To order individual tests, see Celiac Disease Diagnostic Testing Algorithm in Special Instructions.
Evaluating patients suspected of having celiac disease; this includes patients with symptoms compatible with celiac disease, patients with atypical symptoms, and individuals at increased risk of celiac disease
Evaluating the response to treatment with a gluten-free diet
Positive test results for deamidated gliadin antibodies, IgA or IgG, are consistent with the diagnosis of celiac disease.
Negative results indicate a decreased likelihood of celiac disease.
Decreased levels of deamidated gliadin antibodies, IgA or IgG, following treatment with a gluten-free diet are consistent with adherence to the diet. Persistence of high levels of antibodies following dietary treatment suggest poor adherence to the diet or the presence of refractory disease.
Measurements of deamidated gliadin antibodies should not be relied upon exclusively to establish or rule out the diagnosis of celiac disease.
This test should not be ordered as a replacement for TSTGP / Tissue Transglutaminase (Ttg) Antibodies, IgA and IgG Profile, Serum.
Negative: <20.0 U
Weak positive: 20.0-30.0 U
Positive: >30.0 U
Reference values apply to all ages.
1. Green PH, Cellier C: Celiac disease. New Eng J Med 2007;357:1731-1743
2. Green PH, Jabri B: Celiac disease. Annu Rev Med 2006;57:207-221
3. Harrison MS, Wehbi M, Obideen K: Celiac disease: More common than you think. Cleve Clinic J Med 2007;74:209-215
4. Dale JC, Homburger HA, Masoner DE, Murray JA: Update on celiac disease: New standards and new tests. Mayo Communique 2008;33(6):1-9
5. Rashtak S, Ettore MW, Homburger HA, Murray JA: Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin Gastroenterol Hepatol 2008 Apr;6(4):426-432
6. Sugai E, Vazquez H, Nachman F, et al: Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease. Clin Gastroenterol Hepatol 2006;4:1112-1117