Anti-gliadin antibodies are produced in response to gliadin, a prolamin found in
wheat. In bread wheat it is encoded by three different alleles, AA, BB, and DD.
These alleles can produce slightly different gliadins, which can cause the
body to produce different antibodies. Some of these antibodies can detect
proteins in specific grass taxa such as Triticeae, while others react
sporadically with certain species in those taxa, or over many taxonomically
defined grass tribes. Subtypes
= Anti-gliadin IgA = This antibody is found in ~80% of
patients with coeliac disease. It is directed against the alpha/beta and
gamma gliadins. It is also found in a number of patients who are not
enteropathic. Some of these patients may have neuropathies that respond favorably
to a gluten elimination diet. This is referred to as gluten-sensitive
idiopathic neuropathy. Clinically these antibodies and IgG antibodies to gliadin
are abbreviated as AGA. = Anti-gliadin IgG =
The IgG antibody is similar to AGA IgA, but is found at higher levels in
patients with the IgA-less phenotype. It is also associated with coeliac disease
and non-celiac gluten sensitivity. Anti-gliadin antibodies are frequently
found with anti-transglutaminase antibodies.
= Anti-gliadin IgE = The IgE antibodies are more typically
found in allergy-related conditions such as urticaria, asthma, and
wheat-dependent exercise-induced anaphylaxis. The target of the most
allergenic antibodies is ω-5 gliadin, which is encoded by the Gli-1B gene
found on the B haplome of wheat. Anti-gliadin antibodies and the
gluten-free diet What is the relationship of gluten and
anti-gliadin antibodies?. In gluten-sensitive individuals AGA testing
is a routinely used blood test for possible presence of coeliac disease,
allergies or idiopathic phenomena. The measurement of AGA is done with ELISA or
radioimmunoassay. Such tests measure the level of AGA relative to a standard,
such as a level of 10 = point which 85% of normal population falls below.
Greater than 10 equals disease and a value of 3 is expected.
Individuals who have coeliac disease may have values in excess of 200. There is
the common expectation that removal of gluten results in the loss of AGA;
however, since gluten is the target of the antibodies, that which would deplete
them from the body, removal of gluten results in the benign circulation of
antibodies. The half life of these antibodies is typically 120 days. Given
an expected normal of 3 and assuming that the individual starts with a score
of 203, we can predict the levels of AGA at various future time points. Based on
these initial numbers, patients with very high AGA values may take 2 years to
return to the normal range. Refractory coeliac disease. RCD or
non-strict gluten-free diet are two causes of failure of AGA to return to
normality on the GF diet. In the first instance lymphocytes may remain
stimulated even though the antigen that originally stimulated them was removed
from the diet. Diagnostic serology
Anti-gliadin antibodies were one of the first serological markers for coeliac
disease. Problematic with AGA is the typical sensitivity and specificity was
about 85%. Gliadin peptides which are synthesized as the deamidated form have
much higher sensitivity and specificity, creating 2 serological tests for CD that
approach biopsy diagnostic in performance.
Uses of anti-gliadin antibodies in testing
Anti-gliadin antibodies can be generated in mice or rabbits by immunizing whole
purified gliadins, proteolytic fragments of gliadin, or synthetic peptides that
represent epitopes of gliadin. After developing an immune response, B-cells
from mice can be fused with immortalizing cells to form a hybridoma
that produces monoclonal antibodies. Mab can be expressed in culture or via
ascites fluid production to produce large amounts of a single antibody
isoform. Mab can be used to detect levels of
gluten in food products. Some of these antibodies can recognize only wheat
prolamins or very closely related grass seeds; others can detect antigens over
broad taxa. The G12 antibody is the newest example which detects the most
immunotoxic fragment, a 33-mer peptide from �-2 gliadin; available from Romer
Laboratories and the Spanish company Biomedal. It recognizes the toxic
fraction of wheat, barley, rye and also of oat.
The R5 sandwich assay is another such assay. This assay can recognize wheat,
barley and rye, which makes it ideal for evaluating the presence of contaminants
in gluten-free foods that do not contain oat. This antibody is a recommended
testing protocol in a proposed revision of the Codex Alimentarius.
The new standards came about in part because of new sensitive and specific
testing procedures. These procedures are capable of detecting wheat or multiple
cereals at concentrations as low as 1 part per million. A new barley-sensitive
ELISA called the R5 sandwich assay does not detect gluten in any of 25 pure oat
varieties, but it does detect barley, wheat and rye.
References