Coeliac serology
Discuss serologic tests for coeliac disease?
- The best available tests are the IgA antihuman tissue transglutaminase (TTG) and IgA endomysial antibody immunofluorescence (EMA) tests. They have equivalent diagnostic accuracy with sensitivity and specificity of these two tests exceeding 95%.
- These tests may not be as accurate in the clinical setting. Thus, in symptomatic individuals in whom there is strong clinical evidence for CD, a D2 biopsy should be considered even if the serologic test is negative.
- The serologic tests for CD are IgA based and hence will not be able to identify individuals who have both CD and selective IgA deficiency. Approximately 5-10% of celiac patients are IgA deficient. Here, IgG-based tests may be used; however, their accuracy remains to be determined. Thus, D2 biopsies may be best in symptomatic IgA deficient patients.
- Serologic testing for celiac disease in children younger than 5 years of age may be less reliable.
- There are no data to show that a combination of tests is better than a single test using either EMA IgA or TTG IgA.
- Antigliadin antibody (AGA) tests are no longer routinely recommended because of their lower sensitivity and specificity.
Discuss the pathogenesis for coeliac antibodies?
The enzyme tissue transglutaminase (tTG) has an important role in the breakdown of proteins in the small intestine. Dietary gliadin triggers the formation of a gliadin peptide–tTG complex in the small intestine. In CD, antibodies to this peptide-tTG complex (anti-tTG antibodies) are formed, leading to mucosal inflammation.
Discuss the TTG and EMA tests?
- IgA class EMA is measured qualitatively by subjective assessment of direct immunofluorescence with monkey oesophagus or human umbilical cord as the antigenic substrate. This needs experienced microscopists and the assay can only be semi-quantitative at best, using serial dilution titers.
- In contrast, IgA anti-tTG antibody is measured by solid phase ELISA, which is fully quantitative, automated and more reproducible between laboratories. Human recombinant anti tTG is used as the antigenic substrate. These factors allow for reliable, simple, serial measurements of antibody concentration.
Discuss the role of HLA typing in coeliac disease?
Almost 100% of pts with CD have HLA DQ2 or DQ8. However, approximately 30% of the general population is also positive for the DQ2 haplotype. Thus HLA typing would not be very specific, but a negative test for both HLA DQ2 and DQ8 virtually excludes CD.
This may be clinically useful, if duodenal histology is not possible in a patient with positive coeliac serology.
Discuss coeliac serology as a marker of dietary compliance?
- Coeliac serology can be used as an approximate marker of dietary compliance, although a decrease in titer does not correlate with histopathologic improvement.
- In those whose antibody levels do not decrease within 12 months, dietary compliance should be checked and repeat biopsy examination should be performed as necessary by mutual consent.
- Because of the false positivity of tTG and EMA with other autoimmune diseases, such as type 1 diabetes and autoimmune hepatitis, these antibodies may remain elevated in a certain subset of patients despite strict adherence to a GFD.
