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Diagnostic Testing Algorithms for Celiac Disease


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Slide 10

updated June 2011

Because of the prevalence of IgA deficiency in patients with celiac disease, the algorithm begins with assessment of total IgA levels.

If the IgA levels are within the age-adjusted reference range, the patient is identified as not having an IgA deficiency; the most appropriate second level of testing in the context of celiac disease would be for TTG antibodies of the IgA isotype.

If this test result is positive, a diagnosis of celiac disease is possible, and the recommendation is to proceed to a biopsy of the small intestine.

In a case like this, no other serologic testing or HLA typing is necessary.

On the other hand, if the TTG IgA antibody test is negative, a diagnosis of celiac disease is very unlikely.  However, it is important to remember that a certain percentage of patients with celiac disease may be seronegative.  If the testing for TTG IgA antibody is negative, but celiac disease is highly suspected based on clinical presentation or perhaps a family history, the most appropriate test with which to proceed would the HLA-DQ2 and DQ8 typing.  I will expand upon the interpretation of these test results in a moment.

If the result for the TTG IgA antibody test falls in the weakly positive range, further serologic testing may be of use, specifically the deamidated gliadin IgA antibody and the EMA test.

If either the EMA or deamidated gliadin IgA tests are positive, then a biopsy of the small intestine would be warranted.

If both the EMA and deamidated gliadin IgA tests are negative, then it is possible that the result from the TTG IgA antibody test was a false positive, and it is unlikely that the patient has celiac disease.  However, as stated before, some patients with celiac disease may be seronegative.  If celiac disease is highly suspected, then HLA-DQ2 and DQ8 typing would be appropriate.

The test for celiac disease HLA typing identifies the DQ alpha and beta chains that correspond to the DQ2 and DQ8 alleles.

If neither DQ2 nor DQ8 is identified in the patient, celiac disease is almost conclusively excluded as a diagnosis.

On the other hand, if either DQ2 or DQ8 are present, then a diagnosis of celiac disease is possible.

In this case, if the clinical symptoms are strongly suggestive, then proceeding with a biopsy would be suggested.

That covers the pathways in the algorithm that apply to patients with normal concentrations of total IgA.  Let’s move on now to individuals with low total IgA concentrations.  There are 2 possible scenarios.

Individuals may have a detectable amount of total IgA, which is greater than 1 mg/dL, but below the age-adjusted reference range.  For these individuals, the recommended testing is TTG and deamidated gliadin antibodies, both IgA and IgG isotypes.

If the patient has completely undetectable IgA, this would be defined as a selective IgA deficiency.

For these patients, testing for celiac disease should include TTG and deamidated gliadin antibodies, but only the IgG isotypes.

In addition, for patients with selective IgA deficiency who have a history of recurrent infections, further testing for a possible immunodeficiency is warranted.  As an initial evaluation, IgG subclasses and total IgG and IgM, in addition to the total IgA, should be assessed.

Coming back to the celiac disease algorithm, if all the TTG and deamidated gliadin antibody tests are negative in these individuals, then celiac disease becomes an unlikely diagnosis.  For individuals in whom the disease is highly suspected, HLA typing may be informative.

On the other hand, if any of the specific antibody test results are equivocal or positive, the patient should undergo a small intestinal biopsy. Following the biopsy, it is important to consider the pathology results in the context of the serology lab data.

If the biopsy of the patient is positive, meaning it shows evidence of villous atrophy, and the serology for more one or more specific antibodies is positive, then a presumptive diagnosis of celiac disease is established.

However, if the biopsy was performed based on positive serology and the pathology comes out to be negative, then we have a situation where the results are not conclusive.

For these cases, HLA typing is appropriate if it had not been previously performed.

If the HLA typing is negative for both DQ2 and DQ8, then both the biopsy and HLA result indicate that celiac disease is not a probable diagnosis.  This likely means that the serology result was a false positive.

If the patient is positive for DQ2 or DQ8, then celiac disease remains a possibility.  In this case, both the serology and HLA results are positive, but the biopsy is negative.  If the patient is symptomatic, the biopsy may represent a false negative and the patient may, in fact, have a sensitivity to gluten.  If the patient is asymptomatic, the negative biopsy may accurately reflect the fact that the patient’s small intestinal villae have not been exposed to an inflammatory response.  However, given the positive serology and compatible HLA type, these patients should be followed for possible future development of active celiac disease.



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