Coeliac Antibodies

Diagnostic Use

Coeliac disease (CD) is a gluten sensitive enteropathy that is characterized by inflammation and histological flattening of intestinal mucosa, resulting in a malabsorption syndrome (diarrhoea and weight loss), however it may present with less specific findings including anaemia, rashes, depression or osteoporosis. The disease is caused by an immunological response to gluten in genetically susceptible individuals.

Interpretation

Coeliac disease (CD) is a gluten sensitive enteropathy that is characterized by inflammation and histological flattening of intestinal mucosa, resulting in a malabsorption syndrome (diarrhoea and weight loss), however it may present with less specific findings including anaemia, rashes, depression or osteoporosis. The disease is caused by an immunological response to gluten in genetically susceptible individuals.

One of the major protein components of gluten is gliadin; when it meets tissue transglutaminase (tTG) in the intestinal lumen the gliadin peptide undergoes modification, termed deamidation. The negatively charged deamidated gliadin peptide (DGP) then adheres much more strongly to HLA-DQ2 and HLA-DQ8 expressed on antigen presenting cells (APCs). The APCs present antigen to the pro-inflammatory T cells which drive inflammation, subsequent tissue damage and the formation of tTG and DGP antibodies (coeliac serology).

The detection of tTG IgA antibodies is the preferred serological test in diagnosing CD due to its superior sensitivity and specificity. The detection of tTG IgA correlates well with the detection of endomysial antibodies with the additional benefit of semi-quantitative reporting. However selective IgA deficiency is more likely to co-exist with CD 2% vs 0.2% in non-CD and the clinical utility of IgA based assays in young children is also limited. Therefore dual isotype (IgA and IgG) testing is recommended.

Our laboratory uses a sensitive and specific screening strategy for detecting people with CD which includes tTG IgA and DGP IgG therefore total IgA measurements are no longer routinely performed as part of our serological assessment of coeliac disease. The DGP IgG assays differ from conventional gliadin antibody tests which should not be used for CD diagnosis due to poor sensitivity and specificity.

When being used for diagnosis, Coeliac serology is only reliable if performed while the patient is on a gluten containing diet.

Endoscopy and duodenal biopsy remains the gold standard for the diagnosis of CD however as serological testing has improved it is now considered to be an acceptable alternative in some cases.  In 2012 the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) advocate the use of highly sensitive and specific serological testing in combination with HLA typing and clinical symptoms to diagnose CD in paediatric populations.

Genetic susceptibility requires the expression of HLA-DQ2, or HLA-DQ8 on the surface of antigen presenting cells.  Whilst negative testing for these HLA haplotypes virtually excludes a diagnosis of CD, these alleles are quite commonly expressed in the community in both normal and affected individual.

HLA testing can be useful to exclude coeliac disease in individuals who are unable to tolerate gluten containing diet and in those individuals with low positive serological test results.

Reference Intervals

tTG IgA (tissue transglutaminase)

DGP IgG (demidated gliadin peptide)