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HelpTest Code CDSP Celiac Disease Serology Cascade, Serum
Reporting Name
Celiac Disease Serology CascadeUseful 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)
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| IGA | Immunoglobulin A (IgA), S | Yes | Yes |
| CDSP1 | Celiac Disease Interpretation | No | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| EMA | Endomysial Abs, S (IgA) | Yes | No |
| DAGL | Gliadin(Deamidated) Ab, IgA, S | Yes | No |
| TTGG | Tissue Transglutaminase Ab, IgG, S | Yes | No |
| DGGL | Gliadin(Deamidated) Ab, IgG, S | Yes | No |
| TTGA | Tissue Transglutaminase Ab, IgA, S | Yes | No |
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.
The following algorithms are available:
Method Name
Nephelometry
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
SerumOrdering Guidance
This cascade should not be used in patients who have previously been or are currently being treated with a gluten-free diet. For these individuals, order CDGF / Celiac Disease Gluten-Free Cascade, Serum and Whole Blood.
This cascade should not be used in individual who are negative for HLA-DQ2 or DQ8, as a diagnosis of celiac disease is unlikely. For individuals who are positive for either HLA-DQ2 and/or DQ8, this test may be ordered to assess for the presence of autoantibodies associated with celiac disease.
Cascade testing is recommended 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.
-CDCOM / Celiac Disease Comprehensive Cascade, Serum and Whole Blood: Complete testing including HLA DQ
-CDSP / Celiac Disease Serology Cascade, Serum: Complete serology testing excluding HLA DQ
-CDGF / Celiac Disease Gluten-Free Cascade, Serum and Whole Blood: For patients already adhering to a gluten-free diet
To order individual tests, see Celiac Disease Diagnostic Testing Algorithm
Specimen Required
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 5 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 14 days | |
| Frozen | 21 days |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | OK |
Special Instructions
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
≥18 years: 61-356 mg/dL
Day(s) Performed
Profile tests: Monday through Friday; Reflex tests: Monday through Saturday
CPT Code Information
82784
86258 (if appropriate)
86364 (if appropriate)
86231 (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CDSP | Celiac Disease Serology Cascade | 94494-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| IGA | Immunoglobulin A (IgA), S | 2458-8 |
| 28991 | Celiac Disease Interpretation | 69048-7 |
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.
See Celiac Disease Diagnostic Testing Algorithm 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
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.
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.
Method Description
Immunoglobulin A:
Total IgA levels are measured by immunonephelometry. In this Siemens Nephelometer II method, the light scattered onto the antigen-antibody complexes is measured. The intensity of the measured scattered light is proportional to the amount of antigen-antibody complexes in the sample under certain conditions. If the antibody volume is kept constant, the signal behaves proportionally to the antigen volume. A reference curve is generated by a standard with a known antigen content on which the scattered light signals of the samples can be evaluated and calculated as an antigen concentration. Antigen-antibody complexes are formed when a sample containing antigen and the corresponding antiserum are put into a cuvette. A light beam is generated with a light emitting diode, which is transmitted through the cuvette. The light is scattered onto the immuno-complexes that are present. Antigen and antibody are mixed in the initial measurement, but no complex is formed yet. An antigen-antibody complex is formed in the final measurement. The result is calculated by subtracting value of the final measurement from the initial measurement. The distribution of intensity of the scattered light depends on the ratio of the particle size of the antigen-antibody complexes to the radiated wavelength.(Instruction manual: Siemens Nephelometer II, Siemens, Inc.; Version 3, 2008; Addendum to the Instruction Manual 2.3, 08/2017)
Tissue Transglutaminase IgA/IgG Antibodies:
IgA and IgG antibodies to tissue transglutaminase (tTG) are detected by enzyme-linked immunosorbent assay (ELISA). Recombinant human tTG antigen expressed in Escherichia coli is adsorbed to wells of a microtiter plate under conditions that preserve the native state of the antigen. Diluted patient sera are added to the microtiter plate wells under conditions that allow binding of the antibodies to the tTG antigen. Unbound sample constituents are washed away, and horseradish peroxidase (HRP)-labeled antihuman IgA or IgG antibody conjugate is added to each well. After a second incubation, unbound HRP-label is removed, and bound conjugate is detected by adding tetramethylbenzidine (TMB) chromogenic substrate. After a final incubation, colored product is measured spectrophotometrically; the absorbance of the patient sample is compared to the positive calibrator. The absorbance is directly proportional to the level of IgA or IgG antibodies to tTG, which is expressed in arbitrary units.(Package inserts: QUANTA Lite R h-tTG IgA and IgG. Inova Diagnostics, Inc; rev. 8, 01/2020)
Deamidated Gliadin IgA/IgG Antibodies:
IgA and IgG antibodies to deamidated gliadin peptides are detected by ELISA. Purified peptides are adsorbed to wells of a microtiter plate under conditions that preserve the native state of the antigen. Diluted patient sera are added to the microtiter plate wells under conditions that allow binding of the antibodies to the deamidated gliadin peptides. Unbound sample constituents are washed away and HRP-labeled antihuman IgA or IgG antibody conjugate is added to each well. After a second incubation, unbound HRP-label is removed, and bound conjugate is detected by adding TMB chromogenic substrate. After a final incubation, colored product is measured spectrophotometrically; the absorbance of the patient sample is compared to the positive calibrator. The absorbance is directly proportional to the level of IgA or IgG antibodies to deamidated gliadin peptides, which is expressed in arbitrary units.(Package inserts: QUANTA Lite Gliadin IgA II; rev.2, 10/2019; QUANTA Lite Gliadin IgG II. INOVA Diagnostics, Inc; Rev.4, 05/2020)
Endomysial IgA Antibody:
Endomysial IgA antibodies are detected by indirect immunofluorescence assay. Frozen sections of rhesus monkey esophagus substrate are overlaid with dilutions of patient sera and incubated. After washing, the slides are overlaid with fluorescein-conjugated IgA antisera and incubated. After a final washing, the slides are analyzed through fluorescence microscopy.(Sheppard AL, Elwenspoek MMC, Scott LJ, et al: Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease. Aliment Pharmacol Ther. 2022 Mar;55(5):514-527. doi: 10.1111/apt.16729)