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Celiac Disease Serology Cascade, Serum
Test CodeCDSP
Alias/See Also
Epic: LAB8685
Mayo: CDSP
Mayo: CDSP
CPT Codes
82784
Includes
Immunoglobulin A (IgA), S
Celiac Disease Interpretation
TESTING ALGORITHM
If the IgA result is within the age-specified normal range, then tissue transglutaminase (tTG) IgA antibody testing will be performed at an additional charge.
If the tTG IgA antibody result is equivocal, then endomysial IgA and deamidated gliadin IgA antibody testing will be performed at an additional charge.
If the IgA result is greater or equal to 1.0 mg/dL but lower than the age-specified normal range, then tTG IgA, tTG IgG, deamidated gliadin IgA, and deamidated gliadin IgG antibody testing will be performed at an additional charge.
If the IgA result is below the limit of detection (<1.0 mg/dL), then tTG IgG and deamidated gliadin IgG antibody testing will be performed at an additional charge.
Celiac Disease Interpretation
TESTING ALGORITHM
If the IgA result is within the age-specified normal range, then tissue transglutaminase (tTG) IgA antibody testing will be performed at an additional charge.
If the tTG IgA antibody result is equivocal, then endomysial IgA and deamidated gliadin IgA antibody testing will be performed at an additional charge.
If the IgA result is greater or equal to 1.0 mg/dL but lower than the age-specified normal range, then tTG IgA, tTG IgG, deamidated gliadin IgA, and deamidated gliadin IgG antibody testing will be performed at an additional charge.
If the IgA result is below the limit of detection (<1.0 mg/dL), then tTG IgG and deamidated gliadin IgG antibody testing will be performed at an additional charge.
Preferred Specimen
Specimen Type: Serum
Collection Container: Serum gel
Specimen Volume: 5 mL
Minimum Volume
2 mL
Other Acceptable Specimens
Collection Container: Red top
Transport Container
Plastic vial
Specimen Stability
Room temperature: Unacceptable
Refrigerated: 14 days
Frozen: 21 days
Reject Criteria (Eg, hemolysis? Lipemia? Thaw/Other?)
Gross hemolysis, Gross lipemia
Methodology
Nephelometry
Setup Schedule
Profile tests: Monday through Friday;
Reflex tests: Monday through Saturday
Reflex tests: Monday through Saturday
Report Available
7 to 9 days
Limitations
CAUTIONS
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 for whom a small intestinal biopsy is recommended.
This cascade should not be used in patients who have previously been or are currently being treated with a gluten-free diet. See Ordering Guidance.
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 for whom a small intestinal biopsy is recommended.
This cascade should not be used in patients who have previously been or are currently being treated with a gluten-free diet. See Ordering Guidance.
Reference Range
REFERENCE VALUES
Immunoglobulin A (IgA)
0-<5 months: 7-37 mg/dL
5-<9 months: 16-50 mg/dL
9-<15 months: 27-66 mg/dL
15-<24 months: 36-79 mg/dL
2-3 years: 27-246 mg/dL
4-6 years: 29-256 mg/dL
7-9 years: 34-274 mg/dL
10-14 years: 42-295 mg/dL
13-15 years: 52-319 mg/dL
16-17 years: 60-337 mg/dL
> or =18 years: 61-356 mg/dL
INTERPRETATION
Immunoglobulin A:
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 or high 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 tissue transglutaminase (tTG) and deamidated gliadin antibodies are recommended for the evaluation of celiac disease; tTG IgA, tTG IgG, deamidated gliadin IgA, and deamidated gliadin IgG antibody assays are performed in this cascade. For individuals who have selective IgA deficiency or undetectable levels of IgA, only tTG IgG and deamidated gliadin IgG antibody assays are performed.
tTG IgA/IgG Antibodies:
Individuals positive for tTG antibodies of the IgA isotype likely have celiac disease and a small intestinal biopsy is recommended. For individuals with selective IgA deficiency, testing for tTG antibodies of the IgG isotype is performed. In these individuals, a positive tTG IgG antibody result suggests a diagnosis of celiac disease. However, just as with the tTG IgA antibody, a biopsy should be performed to confirm the diagnosis. 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.
Deamidated Gliadin IgA/IgG Antibodies:
Positivity for deamidated gliadin antibodies of the IgA isotype is suggestive of celiac disease; small intestinal biopsy is recommended. For individuals with selective IgA deficiency, testing for deamidated gliadin antibodies of the IgG isotype is performed. In these individuals, a positive deamidated gliadin IgG antibody result suggests a diagnosis of celiac disease. However, just as with the deamidated gliadin IgA antibody, a biopsy should be performed to confirm the diagnosis. 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.
Endomysial IgA Antibodies:
Positivity for endomysial antibodies (EMA) of the IgA isotype is suggestive of celiac disease, and small intestinal biopsy is recommended. For individuals with selective IgA deficiency, evaluation of EMA is not indicated. Negative EMA 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.
Immunoglobulin A (IgA)
0-<5 months: 7-37 mg/dL
5-<9 months: 16-50 mg/dL
9-<15 months: 27-66 mg/dL
15-<24 months: 36-79 mg/dL
2-3 years: 27-246 mg/dL
4-6 years: 29-256 mg/dL
7-9 years: 34-274 mg/dL
10-14 years: 42-295 mg/dL
13-15 years: 52-319 mg/dL
16-17 years: 60-337 mg/dL
> or =18 years: 61-356 mg/dL
INTERPRETATION
Immunoglobulin A:
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 or high 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 tissue transglutaminase (tTG) and deamidated gliadin antibodies are recommended for the evaluation of celiac disease; tTG IgA, tTG IgG, deamidated gliadin IgA, and deamidated gliadin IgG antibody assays are performed in this cascade. For individuals who have selective IgA deficiency or undetectable levels of IgA, only tTG IgG and deamidated gliadin IgG antibody assays are performed.
tTG IgA/IgG Antibodies:
Individuals positive for tTG antibodies of the IgA isotype likely have celiac disease and a small intestinal biopsy is recommended. For individuals with selective IgA deficiency, testing for tTG antibodies of the IgG isotype is performed. In these individuals, a positive tTG IgG antibody result suggests a diagnosis of celiac disease. However, just as with the tTG IgA antibody, a biopsy should be performed to confirm the diagnosis. 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.
Deamidated Gliadin IgA/IgG Antibodies:
Positivity for deamidated gliadin antibodies of the IgA isotype is suggestive of celiac disease; small intestinal biopsy is recommended. For individuals with selective IgA deficiency, testing for deamidated gliadin antibodies of the IgG isotype is performed. In these individuals, a positive deamidated gliadin IgG antibody result suggests a diagnosis of celiac disease. However, just as with the deamidated gliadin IgA antibody, a biopsy should be performed to confirm the diagnosis. 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.
Endomysial IgA Antibodies:
Positivity for endomysial antibodies (EMA) of the IgA isotype is suggestive of celiac disease, and small intestinal biopsy is recommended. For individuals with selective IgA deficiency, evaluation of EMA is not indicated. Negative EMA 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.
Clinical Significance
USEFUL FOR
Evaluating patients suspected of having celiac disease, including patients with compatible symptoms, patients with atypical symptoms, and individuals at increased risk (family history, previous diagnosis with associated disease, positivity for HLA-DQ2 and/or DQ8)
CLINICAL INFORMATION
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. Common clinical manifestations related to gastrointestinal inflammation include abdominal pain, malabsorption, diarrhea, and/or constipation. 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. 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. The disease is also associated with other clinical disorders including thyroiditis, type I diabetes mellitus, Down syndrome, and IgA deficiency.
Individuals with family members who have celiac disease are at increased risk of developing the disease.(2) Genetic susceptibility is related to specific human leukocyte antigen (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. For this reason, HLA-DQ2 and HLA-DQ8 are considered genetic risk factors for celiac disease and are required, but not sufficient, for the disease process to occur.
A definitive diagnosis of celiac disease requires a jejunal biopsy demonstrating villous atrophy.(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. Because no single laboratory test can be relied upon completely to establish a diagnosis of celiac disease, individuals with positive laboratory results may be referred for small intestinal biopsy, thereby decreasing the number of unnecessary invasive procedures (see Celiac Disease Comprehensive Cascade Test Algorithm). In terms of serology, celiac disease is associated with a variety of autoantibodies, including endomysial antibody, 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. The most sensitive and specific serologic test is tTG IgA isotype, in individuals who produce sufficient total IgA. For Individuals who are IgA deficient, testing for tTG and deamidated gliadin IgG antibodies is required.
The treatment for celiac disease is maintenance of a gluten-free diet. In most patients who adhere to this diet, concentrations of associated autoantibodies decline, which is sometimes also accompanied by reconstitution of the small intestinal villi. In most patients, an improvement in clinical symptoms is observed. 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.
Evaluating patients suspected of having celiac disease, including patients with compatible symptoms, patients with atypical symptoms, and individuals at increased risk (family history, previous diagnosis with associated disease, positivity for HLA-DQ2 and/or DQ8)
CLINICAL INFORMATION
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. Common clinical manifestations related to gastrointestinal inflammation include abdominal pain, malabsorption, diarrhea, and/or constipation. 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. 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. The disease is also associated with other clinical disorders including thyroiditis, type I diabetes mellitus, Down syndrome, and IgA deficiency.
Individuals with family members who have celiac disease are at increased risk of developing the disease.(2) Genetic susceptibility is related to specific human leukocyte antigen (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. For this reason, HLA-DQ2 and HLA-DQ8 are considered genetic risk factors for celiac disease and are required, but not sufficient, for the disease process to occur.
A definitive diagnosis of celiac disease requires a jejunal biopsy demonstrating villous atrophy.(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. Because no single laboratory test can be relied upon completely to establish a diagnosis of celiac disease, individuals with positive laboratory results may be referred for small intestinal biopsy, thereby decreasing the number of unnecessary invasive procedures (see Celiac Disease Comprehensive Cascade Test Algorithm). In terms of serology, celiac disease is associated with a variety of autoantibodies, including endomysial antibody, 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. The most sensitive and specific serologic test is tTG IgA isotype, in individuals who produce sufficient total IgA. For Individuals who are IgA deficient, testing for tTG and deamidated gliadin IgG antibodies is required.
The treatment for celiac disease is maintenance of a gluten-free diet. In most patients who adhere to this diet, concentrations of associated autoantibodies decline, which is sometimes also accompanied by reconstitution of the small intestinal villi. In most patients, an improvement in clinical symptoms is observed. 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.
Performing Laboratory
Mayo Clinic Laboratories - Rochester
3050 Superior Drive NW
Rochester, MN 55901
Additional Information
Mayo Test Info
Celiac Disease Comprehensive Cascade Test Algorithm
Celiac Disease Diagnostic Testing Algorithm
Celiac Disease Gluten-Free Cascade Test Algorithm
Celiac Disease Routine Treatment Monitoring Algorithm
Celiac Disease Serology Cascade Test Algorithm
Last Updated: May 4, 2023
Last Review: N. Wolford, May 4, 2023