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

Reporting Name

Celiac Disease Gluten-Free Cascade

Useful For

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

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 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 developing 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. 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 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. 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, antibody titers may take up to 1 year to normalize. Persistently elevated results suggest poor adherence to the gluten-free diet or the possibility of refractory celiac disease.

 

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

 

For the recommended approach to a patient suspected of celiac disease, see Celiac Disease Diagnostic Testing Algorithm..

 

For monitoring the patient's response to treatment, see Celiac Disease Routine Treatment Monitoring Algorithm.

Interpretation

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:

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/IgG Antibodies:

Individuals positive for tTG antibodies of the IgA and/or IgG isotype may 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 indicated. 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 and/or IgG isotype is suggestive of celiac disease, and a small intestinal biopsy is recommended. For individuals with selective IgA deficiency, testing for deamidated gliadin antibodies of the IgG isotype is indicated. 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.

Profile Information

Test ID Reporting Name Available Separately Always Performed
CELI2 HLA-DQ Typing Yes, (Order CELI) Yes
CDGF1 Celiac Disease Interpretation No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
TTGA Tissue Transglutaminase Ab, IgA, S Yes No
DAGL Gliadin(Deamidated) Ab, IgA, S Yes No
DGGL Gliadin(Deamidated) Ab, IgG, S Yes No
TTGG Tissue Transglutaminase Ab, IgG, S Yes No
IGA Immunoglobulin A (IgA), S Yes No

Testing Algorithm

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

 

For more information see Celiac Disease Gluten-Free Cascade Test Algorithm.

Report Available

9 to 11 days

Day(s) Performed

Profile tests: Monday through Friday; Reflex tests: Monday through Saturday

Clinical Reference

1. Rubin JE, Crowe SE: Celiac disease. Ann Int Med. 2020 Jan;172(1):ITC1-ITC16

2. Lebwohl B, Rubio-Tapia A: Epidemiology, presentation, and diagnosis of celiac disease. Gastroenterology. 2021 Jan;160(1):63-75

3. Rubio-Tapia A, Hill ID, Kelly, CP, Calderwood AH, Murray JA;  American College of Gastroenterology: ACG clinical guidelines: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013 May;108(5):656-676

4. Penny HA, Raju SA, Sanders DS: Progress in the serology-based diagnosis and management of adult celiac disease. Exp Rev Gastroenterol Hepatol. 2020 Mar;14(3):147-154

Method Name

Polymerase Chain Reaction (PCR)/Sequence-Specific Oligonucleotide Probe (SSO)

Specimen Type

Serum
Whole Blood ACD-B


Ordering Guidance


This cascade should not be used in patients for whom human leukocyte antigen (HLA) DQ2/DQ8 typing has already been performed. For individuals who are positive for either DQ2 and/or DQ8, CDSP / Celiac Disease Serology Cascade, Serum should be ordered to assess for the presence 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.

 

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


Both whole blood and serum are required.

 

Specimen Type: Whole Blood

Container/Tube: Yellow top (ACD solution A or B)

Specimen Volume: 6 mL

Collection Instructions: Send whole blood in original tube. Do not aliquot.

 

Specimen Type: Serum

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL

Collection Instructions: Centrifuge and aliquot serum into plastic vial


Specimen Minimum Volume

Blood: 3 mL
Serum: 1.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 21 days
  Frozen  21 days
Whole Blood ACD-B Refrigerated (preferred)
  Ambient 

Reference Values

HLA-DQ TYPING

Presence of HLA-DQ2 or HLA-DQ8 alleles associated with celiac disease

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

81376 x 2

82784 (if appropriate)

86258 (if appropriate)

86364 (if appropriate)

86231 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CDGF Celiac Disease Gluten-Free Cascade 94493-4

 

Result ID Test Result Name Result LOINC Value
DQA DQ alpha 1 94495-9
28991 Celiac Disease Interpretation 69048-7
DQB DQ beta 1 53938-7
CELIG Celiac gene pairs present? 48767-8

Forms

If not ordering electronically, complete, print, and send Gastroenterology and Hepatology Client Test Request (T728) with the specimen

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Behavioral, mml-Movement-Disorders, mml-Neuroimmunology, mml-Pediatric, mml-Spinal-Cord, mml-Neuro-ophthalmology