Diagnosis of celiac disease

6.1. Serological Tests

There is a significant role for serological tests in the diagnosis and management of celiac disease. Antigliadin antibodies (AGA) measured by enzyme-linked immunosorbent assays are a sensitive although nonspecific test for the presence of celiac disease. False-positive gliadin antibodies have been reported in other conditions including small bowel bacterial overgrowth as well as in healthy individuals. This is particularly true for IgG AGA, which has a high false-positive rate. IgA AGA is more specific, but its sensitivity (~80%) is less, in part due to the fact that IgA deficiency is increased in celiacs. The use of antigliadin antibodies in the detection of celiac disease has been recently questioned because of their lower specificity. However, they can play a role in assessing young children in whom tTG assays are less sensitive [45] and in following some celiacs on a gluten-free diet when the tTG levels are slow to decline. Serum antireticulin antibodies (ARA) should no longer be used due to lower sensitivity and specificity.

Endomysial IgA antibody (EMA) reacts with the endomysium or loose connective tissue around smooth muscle bundles and is assayed by immunofluorescence using monkey esophagus or human umbilical cord as the substrate. It is now known that tissue transglutaminase (tTG) is the antigen to which EMA reacts, and ELISAs have been developed that use guinea pig or human recombinant tTG as the antigen. Human sources of tTG are superior to guinea pig as the assay substrate. The sensitivities of EMA and IgA tTG are similar and can approach 98%, although lower levels of sensitivity are reported for EMA testing. Both have lower sensitivity in the presence of lesser degrees of villous atrophy. The EMA is virtually 100% specific, while the tTG IgA specificity is about 95% with false-positive tests reported in autoimmune diseases, liver disease, inflammatory bowel disease and heart failure. The IgG tTG may have value in diagnosing celiac disease in the presence of IgA deficiency, although the literature suggests the sensitivity of this test overall is only 40% on average. However,

Table 6.4

Summary of Serological Tests and their Usefulness in Adults

Table 6.4

Summary of Serological Tests and their Usefulness in Adults

Test

Sensitivity

Specificity

IgA AGA

<80% in 50% of studies

>80% in most studies

IgG AGA

Variable

Non-specific

IgA EMA

96-97% ME 90% HUV

100% ME 100% HUV

IgA tTG

90% GP 98% HR

95% GP 98% HR

IgG tTG

40%

98%

Source: Adapted from Rostom et al. [48]. AGA antigliadin antibody; EMA endomysial antibody; tTG tissue transglutaminase; ME monkey esophagus; HUV human umbilical vein; GP guinea pig; HR human recombinant

Source: Adapted from Rostom et al. [48]. AGA antigliadin antibody; EMA endomysial antibody; tTG tissue transglutaminase; ME monkey esophagus; HUV human umbilical vein; GP guinea pig; HR human recombinant some studies suggest a higher sensitivity of the IgG tTG assay in IgA deficiency. Options to exclude IgA deficiency as a cause for a false-negative serological IgA test include obtaining a total IgA level or assessing the concentration of tTG IgA [46]. Table 6.4 summarizes numerical data regarding the sensitivity and specificity of these serological tests [47, 48].

Antibody tests should not replace intestinal morphology for making a diagnosis of celiac disease, but in those unable or unwilling to undergo endoscopy, the presence of a positive EMA or high titer IgA tTG is most suggestive of the diagnosis of celiac disease. These antibody assays are useful in monitoring compliance since levels will decrease on a gluten-free diet and increase after the ingestion of gluten. tTG or EMA can also play a role in the timing of endoscopy and biopsy during a gluten challenge (Table 6.5) used in diagnosing patients who had been on a gluten-free diet without an initial proven diagnosis of celiac disease. Another potential role for the antibody tests is in screening higher risk individuals including relatives of celiac patients and those with autoimmune conditions including type I diabetics. The optimal antibody or panel of antibodies to use for screening has not been determined and will depend on the prevalence in the population being screened [48]. Intestinal biopsy specimens should be obtained in all individuals with elevated EMA or tTG antibodies wherever possible.

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