Coeliac disease, also known as gluten sensitive
enteropathy, results from immune mediated damage to small bowel mucosa triggered by an
immune response to the gliadin fraction of gluten, a component of wheat, barely and oats
. The pathogenesis of the disease is dependent upon the de-amidation
of proteins within the gliadin fraction by the intestinal enzyme, tissue transglutaminase
(tTG). This modification induces antibodies to both gliadin and tTG. The presence of
auto-antibodies has lead to the development of a number of serological tests which assist
with the diagnosis of coeliac disease. Final diagnosis however, is still dependent on
characteristic histological changes found on small bowel biopsy and improvement on a
gluten free diet.
Autoantibodies in Coeliac disease.
number of antibodies have been described as having an association with Coeliac disease. These include anti-gliadin and
anti-transglutaminase antibodies. The later
can be measured by either immunofluorescence and reported as anti-endomysial antibodies or
by ELISA and reported directly as anti-transglutaminase antibodies. In each case both IgG and IgA isotype antibodies
have been described. In general the IgA
antibodies have greater sensitivity and specificity and are the preferred diagnostic tool.
However, a negative IgA autoantibody result must be interpreted carefully. IgA
deficiency occurs more frequently in patients with Coeliac disease (approx 2%) than in the
normal population (approx 0.15%). Furthermore,
individuals with IgA deficiency have at least a 10 fold increased risk of coeliac disease
than the general population. Therefore the
potential for a false negative IgA based serological test is real and a concurrent IgA
estimation is recommended when ordering coeliac serology. Currently the tests offered by
SYDPATH include, IgA anti-endomysial antibody and IgA and IgG anti gliadin antibodies, but
the IgA based tests are only interpretable if one knows that IgA deficiency is absent.
Detected as anti-endomysial antibodies by indirect immuno-fluorescence on tissue sections: These are measured by indirect
immuno-fluorescence. IgA anti-endomysial antibodies have consistently been shown to have
high sensitivity and specificity for coeliac disease.
This is the most widely used test in Australian laboratories. The major protein stained in this assay is tissue
transglutaminase (tTG). The main technical
problem with this assay is that the presence of concomitant anti-smooth muscle antibody
making the interpretation of the slides more difficult. The presence of a high titre
anti-smooth muscle antibody may make the test uninterpretable and an alternative
serological test should be performed.
Detected by ELISA as anti-transglutaminase antibodies: This assay is an
alternative to the anti-endomysial antibody and has similar levels of sensitivity and
specificity. However it is incompletely
validated and this has limited its widespread adoption. Recent data indicate that low
level reactivity occurs in a range of autoimmune disorders complicating the interpretation
of low titre results.
the parity of the anti-endomysial and anti-tissue transglutaminase assays most laboratories do not offer both. SydPath currently offers the anti-endomysial
ELISA based assay has a lower sensitivity and specificity than the IgA anti-endomysial and
IgA anti-transglutaminase antibody tests. However,
there may be some patients with coeliac disease who have detectable anti-gliadin
antibodies but no antibodies to transglutaminase. The
IgG form of this test is most useful in children less than 2 years of age and in guiding
diagnosis in individuals with IgA deficiency. It
is also used to monitor dietary compliance.
should be used as a guide to identify those who are most likely to have a positive small
bowel biopsy which is required to confirm the diagnosis of coeliac disease. In those older
than 2 years of age, an IgA anti-endomysial antibody is the
test of choice. This ideally should be
ordered in conjunction with a total serum IgA level to exclude IgA deficiency. In those with IgA deficiency then IgG isotype antibodies
against gliadin may be of utility. Diagnostic suspicion must be confirmed by small bowel
biopsy. Adherence to diet can be monitored by anti-gliadin antibody. However,
normalisation of antibody levels does not guarantee resolution of tissue histopathology.
levels should be ordered in those in whom these are not known, as IgA deficiency is more
common in those with coeliac disease and will result in a false negative test.
Antibody testing in IgA deficient
is no diagnostic utility in measuring IgG
isotype autoantibodies in individuals with
normal IgA levels. In IgA deficient individuals measurement
of IgG isotype anti-endomysial, tissue
transglutaminase or gliadin antibodies may be useful.