What does a negative Immunoglobulin A (IgA) gliadin antibody and a low positive Immunoglobulin G (IgG) gliadin antibody indicate in a Celiac disease screen?

From the Guidelines

A negative IgA gliadin antibody with a low positive IgG gliadin antibody in a Celiac disease screen is inconclusive and requires further evaluation to rule out IgA deficiency or other conditions. This pattern could indicate several possibilities: it might represent early Celiac disease, IgA deficiency (where IgG antibodies become more relevant), or a false positive IgG result 1.

Key Considerations

• The presence of a low positive IgG gliadin antibody may suggest an immune response, but it is not specific enough for a definitive diagnosis of Celiac disease.
• IgA deficiency is a common condition that can lead to false-negative results for IgA-based tests, making IgG antibodies more relevant in these cases 1.
• The clinical picture, including symptoms and family history, must be considered alongside laboratory findings to guide further testing and management.

Recommended Approach

• Further testing is necessary to confirm or rule out Celiac disease, including total IgA levels to assess for IgA deficiency, and more specific Celiac markers like tissue transglutaminase (tTG) antibodies and endomysial antibodies (EMA) 1.
• If clinical suspicion remains high despite these results, an intestinal biopsy while on a gluten-containing diet would be the gold standard for diagnosis, as it can provide direct evidence of small bowel damage characteristic of Celiac disease 1.
• It is crucial to continue consuming gluten until testing is complete, as eliminating gluten prematurely can affect test results and lead to false-negative diagnoses 1.

Additional Testing

• Total IgA level measurement to rule out IgA deficiency.
• Testing for anti-tissue transglutaminase, IgA against deamidated gliadin peptide, and endomysial antibody (IgA) to assess for Celiac disease-specific antibodies.
• Consideration of HLA typing to assess genetic risk factors for Celiac disease, although this is more relevant in cases where diagnosis is uncertain and serology is negative 1.

From the Research

Celiac Screen Interpretation

• A negative IgA gliadin antibody and low positive IgG gliadin result in a Celiac screen can be interpreted as follows:
  • The negative IgA gliadin antibody suggests that the patient may not have a typical immune response to gliadin, a protein found in wheat, barley, and rye 2.
  • The low positive IgG gliadin result may indicate a potential immune response to gliadin, but the clinical significance of this result is not entirely clear 3, 4.
• The combination of these results may suggest that the patient has a non-classical or potential Celiac disease, but further testing and evaluation are necessary to confirm the diagnosis 5, 6.

Diagnostic Considerations

• The diagnostic accuracy of IgG gliadin antibodies is generally lower than that of IgA gliadin antibodies, but they may still be useful in certain situations, such as in patients with IgA deficiency 5.
• The addition of IgG gliadin antibodies to the diagnostic panel may increase the sensitivity of Celiac disease diagnosis, particularly in children under two years of age 6.
• However, the specificity of IgG gliadin antibodies is generally lower than that of IgA gliadin antibodies, which may lead to false-positive results 4.

Clinical Implications

• Patients with a negative IgA gliadin antibody and low positive IgG gliadin result should undergo further evaluation, including intestinal biopsy and other diagnostic tests, to confirm or rule out Celiac disease 2, 3.
• A gluten-free diet may be recommended for patients with a potential Celiac disease diagnosis, but this should be done under the guidance of a healthcare professional 5, 6.