26568 Celiac Disease Comprehensive Cascade, Serum and Whole Blood (CDCOM)

Anti-Endomysial Antibody; Antiendomysial Antibody ;Antimesothelial Antibody; Celiac Disease; Coeliac Disease; Dermatitis Herpetiformis; EA; EMA; Failure to Thrive; Gamma-Globulins, Quantitative; Gliadin Antibodies IgA; Gliadin Antibodies IgG; Gliadin IgA, Serum; Gliadin IgG, Serum; Gluten-sensitive Enteropathy; HLA Celiac Disease Testing; IgA (Immunoglobulin A); Immunofluorescence Antibodies; Malabsorption; SOft-CDCOM; Sprue; Tissue Transglutaminase (tTG); Tissue Transglutaminase Ab IgA; Transglutaminase (tTG); Gluten Panel; Transglutaminase Ab IgG​​

​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)

Comprehensive algorithmic evaluation including human leukocyte antigen typing

​Both blood and serum are required

Send whole blood in original tube. Do not aliquot.

Gross hemolysis

Gross lipemia​

​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.

​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. 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 to 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. 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. In terms of serology, celiac disease is associated with a variety of autoantibodies, including endomysial antibody, tissue transglutaminase (tTG), and deamidated gliadin antibodies. 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 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. 

​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 with undetectable levels of IgA, only -tTG IgG and -deamidated gliadin IgG antibody assays are performed.

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. 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. Individuals with DQ2 and/or DQ8 alleles, in the context of positive serology and compatible clinical symptoms, should be referred for small intestinal biopsy. HLA typing may be especially helpful for those patients who have begun to follow a gluten-free diet prior to a confirmed diagnosis of celiac disease.

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, and a 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 Antibody, IgA:
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 antibodies is not indicated. Negative EMA 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.