Test Catalog

Test ID: CDGF    
Celiac Disease Gluten-Free Cascade, Serum and Whole Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluating patients suspected of having celiac disease who are currently (or were recently) on a gluten-free diet

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If HLA-DQ typing is positive or equivocal for DQ2 or DQ8, then IgA, tissue transglutaminase (tTG) IgA and IgG, and deamidated gliadin IgA and IgG will be performed at an additional charge.


The following algorithms are available in Special Instructions:

-Celiac Disease Comprehensive Cascade

-Celiac Disease Diagnostic Testing Algorithm

-Celiac Disease Gluten-Free Cascade

-Celiac Disease Routine Treatment Monitoring Algorithm

-Celiac Disease Serology Cascade

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Celiac disease (gluten-sensitive enteropathy, celiac sprue) results from an immune-mediated inflammatory process following ingestion of wheat, rye, or barley proteins that occurs in genetically susceptible individuals.(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 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 with 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 and genetic laboratory tests may be used to identify individuals with a high probability of having celiac disease. Subsequently, those individuals with positive laboratory results should be referred for small intestinal biopsy, thereby decreasing the number of unnecessary invasive procedures. In terms of serology, 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.


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 (see Celiac Disease Routine Treatment Monitoring Algorithm in Special Instructions). This is typically accompanied by an improvement in clinical symptoms.


It should be noted that HLA typing is not required to establish a diagnosis of celiac disease. Consider ordering CDSP / Celiac Disease Serology Cascade if HLA typing is not desired or has been previously performed.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


Presence of DQ2 or DQ8 alleles associated with celiac disease

Interpretation Provides information to assist in interpretation of the test results

HLA-DQ Typing:

Approximately 90% to 95% of patients with celiac disease have the HLA-DQ2 allele; most of the remaining patients with celiac disease have the HLA-DQ8 allele. Individuals who do not carry either of these alleles are unlikely to have celiac disease. For these individuals, no further serologic testing is required. However, individuals with these alleles may not, during their lifetime, develop celiac disease. Therefore, the presence of DQ2 or DQ8 does not conclusively establish a diagnosis of celiac disease. For individuals with DQ2 and/or DQ8 alleles, in the context of positive serology and compatible clinical symptoms, small intestinal biopsy is recommended.


Immunoglobulin A (IgA):

Total IgA levels below the age-specific reference range suggest either a selective IgA deficiency or a more generalized immunodeficiency. For individuals with a low IgA level, additional clinical and laboratory evaluation is recommended. Some individuals may have a partial IgA deficiency in which the IgA levels are detectable, but fall below the age-adjusted reference range. For these individuals, both IgA and IgG isotypes for tTG and deamidated gliadin antibodies are recommended for the evaluation of celiac disease.


Tissue Transglutaminase (tTG) Antibody, IgA/IgG:

Individuals positive for tTG antibodies of the IgA and/or IgG isotype may have celiac disease and small intestinal biopsy is recommended. Negative tTG IgA and/or IgG antibody serology does not exclude a diagnosis of celiac disease, as antibody levels decrease over time in patients who have been following a gluten-free diet.


Gliadin (Deamidated) Antibody, IgA/IgG:

Positivity for deamidated gliadin antibodies of the IgA and/or IgG isotype is suggestive of celiac disease, and small intestinal biopsy is recommended. Negative deamidated gliadin IgA and/or IgG antibody serology does not exclude a diagnosis of celiac disease, as antibody levels decrease over time in patients who have been following a gluten-free diet.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This cascade should not be solely relied upon to establish a diagnosis of celiac disease. It should be used to identify patients who have an increased probability of having celiac disease and for whom a small intestinal biopsy is recommended.


This cascade is designed for use in patients who have already instituted, or recently discontinued, a gluten-free diet. For patients who are not following a gluten-free diet, CDCOM / Celiac Disease Comprehensive Cascade is the preferred test.


This cascade should not be used in patients for whom HLA DQ2/DQ8 typing has already been performed. For individuals who are positive for either DQ2 and/or DQ8, CDSP / Celiac Disease Serology Cascade should be ordered to assess the levels of autoantibodies associated with celiac disease. For individuals who are negative for DQ2 and DQ8, no further testing is necessary as a diagnosis of celiac disease is unlikely.

Supportive Data

See individual test IDs

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Green PHR, Cellier C: Medical progress: Celiac disease. N EngL J Med 2007;357:1731-1743 

2. Green PHR, Jabri J: Celiac disease. Ann 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. Update on celiac disease: New standards and new tests. Mayo Communique (2008)

Special Instructions Library of PDFs including pertinent information and forms related to the test