Antigliadin antibodies (AGA) are specific proteins produced by the immune system in response to gliadin, a component of gluten. These antibodies were historically among the first blood markers used in testing for gluten-related disorders. The presence of AGA in a blood test indicates that the body’s immune system is reacting to the gliadin protein.
Understanding Gliadin
Gliadin is a type of prolamin, a storage protein found primarily in wheat, but also in related grains like barley and rye. When gluten is consumed, digestion breaks it down into components like gliadin and glutenin. Gliadin contains high amounts of the amino acids proline and glutamine, making it highly resistant to complete digestion by human enzymes in the small intestine.
This incomplete breakdown results in long, indigestible gliadin peptides, or fragments, that can cross the intestinal lining. In genetically susceptible individuals, these peptides interact with immune cells, triggering an inappropriate immune response because the body perceives the undigested protein as a foreign invader. This interaction is the root cause of the inflammation seen in gluten-sensitive conditions.
The Function of Antigliadin Antibodies
When the immune system detects these gliadin fragments, it produces specific Antigliadin Antibodies (AGA) to bind to the protein, tagging it for immune clearance. Clinicians typically test for two distinct classes of these antibodies: Immunoglobulin A (IgA) and Immunoglobulin G (IgG).
The IgA class of AGA is generally associated with active inflammatory processes within the gut lining and is often linked to the ongoing consumption of gluten. The IgG class is considered a less specific marker and can be present in individuals who may have a gluten sensitivity that does not involve the severe intestinal damage seen in other conditions. IgG-AGA is also particularly relevant for individuals who have a selective IgA deficiency, a condition where the body cannot produce IgA antibodies effectively.
The measurement of these antibodies signals a reaction to gliadin but is not a direct measure of intestinal damage. The overall sensitivity of the original AGA test for detecting conditions like celiac disease was around 80%, which is lower than newer markers.
Interpreting Test Results
A positive result for an Antigliadin Antibody test means the measured levels of IgA-AGA or IgG-AGA in the blood are above the established reference range. This finding suggests an immune reaction to the gliadin component of gluten is occurring and serves as a screening indicator for a gluten-related disorder.
AGA testing is not considered diagnostic on its own due to its limited specificity. A positive result can occur in individuals with conditions other than celiac disease, such as Crohn’s disease, ulcerative colitis, or non-celiac gluten sensitivity. A negative AGA result suggests a gluten-related disorder is less likely, but does not entirely rule it out.
For accurate interpretation, the test must be performed while the patient is still consuming a gluten-containing diet. If a positive result is found, it usually necessitates further investigation, potentially involving additional blood tests or an intestinal biopsy, to determine the exact cause of the immune reaction.
The Shift to Modern Diagnostic Markers
The use of Antigliadin Antibodies has largely been replaced or supplemented by newer, more accurate serological markers in clinical practice. The primary limitation of the original AGA test was its tendency to produce false-positive results in people who did not have celiac disease, reducing its reliability as a definitive marker. This led to the adoption of tests that target more specific immune responses.
The most widely accepted modern test is for tissue Transglutaminase antibodies (tTG), which target an enzyme involved in the disease process, offering higher sensitivity and specificity. Another highly utilized test is for Deamidated Gliadin Peptide antibodies (DGP). DGP antibodies target gliadin fragments that have been chemically modified by the tTG enzyme in the body, which makes them a more specific target than the original, unmodified gliadin protein.
The DGP test is considered a significant improvement over the original AGA test because it focuses on a modified form of gliadin that is more directly implicated in the immune response. Using DGP-IgG is particularly valuable when testing patients with IgA deficiency, who would otherwise test falsely negative on an IgA-based tTG test. The combination of tTG-IgA and DGP-IgG assays provides a robust and highly sensitive approach for screening for gluten-related disorders.