Celiac Disease Gluten-Free Cascade
Evaluating patients suspected of having celiac disease who are currently (or were recently) on a gluten-free diet
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.
See individual test IDs
Clinical Reference Provides recommendations for further 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)