What is the next step to rule out celiac disease in a patient with a celiac panel showing low Immunoglobulin A (IgA)?

From the Guidelines

The next step to rule out celiac disease in a patient with low Immunoglobulin A (IgA) is to order HLA genetic testing to determine whether the patient carries an HLA genotype (DQ2 or DQ8) that is compatible with developing celiac disease, as recommended by the most recent study 1. This approach is supported by the latest evidence, which suggests that HLA testing is most helpful for patients if results are negative, as this excludes the possibility of seronegative celiac disease as a diagnosis. Some key points to consider in the diagnostic process include:

• Low IgA levels can cause false-negative results on standard IgA-based celiac tests, and approximately 2-3% of celiac patients have selective IgA deficiency.
• HLA genetic testing can be particularly useful in cases when seronegative enteropathy is present, the diagnostic workup for celiac disease is not complete, and the patient has already initiated a gluten-free diet and reports severe symptoms with gluten exposure.
• A negative result for HLA DQ2 and DQ8 would confirm that celiac disease is not present, preventing the patient from undergoing a gluten challenge, an unnecessary trial of the gluten-free diet, and further diagnostic workup for celiac disease.
• Clinicians should carefully evaluate for HLA DQ2.5 (DQA10501, DQB10201), HLA DQ8 (DQA103, DQB10302), HLA DQ 2.2 (DQA10201, DQB10202) and HLA DQ7.5 (DQA105, DQB10301) and review whether half heterodimers, which are compatible with celiac disease, are present before determining that a patient is HLA-negative, as suggested by the study 1. However, it's also important to consider other recent studies, such as 1 and 1, which provide additional guidance on the diagnosis and management of celiac disease, including the use of IgG-based celiac serologies and endoscopic duodenal biopsy. Ultimately, the choice of next step will depend on the individual patient's circumstances and the clinical suspicion of celiac disease.

From the Research

Next Steps to Rule Out Celiac Disease

In a patient with a celiac panel showing low Immunoglobulin A (IgA), the next steps to rule out celiac disease involve considering the patient's IgA deficiency, which is more common in individuals with celiac disease than in the general population 2.

• IgA Deficiency Consideration: Given that IgA deficiency can lead to false-negative serology results in celiac disease diagnosis, it is crucial to assess for IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) as alternative markers for celiac disease in IgA-deficient individuals 3.
• Serological Tests: The measurement of IgG transglutaminase antibodies can be a reliable diagnostic tool for celiac disease, especially when IgA is low or deficient 4. IgG anti-tTG seems to be a more reliable marker for CD in IgA deficient adults, whereas the diagnostic specificity of anti-DGP appears to be lower 3.
• Small Bowel Biopsy: Although serological tests are preferred for initial screening, a small bowel biopsy followed by a favorable clinical and serological response to a gluten-free diet can confirm the diagnosis of celiac disease 5.
• HLA Typing and Clinical Presentation: Considering the patient's HLA typing and clinical presentation can also aid in the diagnosis. HLA-DQ2/DQ8 positivity is common in individuals with celiac disease, and certain clinical presentations may increase the suspicion for celiac disease 5, 3.

Diagnostic Approach

The diagnostic approach for celiac disease in patients with low IgA involves:

• Assessing IgG antibodies to tissue transglutaminase and gliadin to identify potential celiac disease in IgA-deficient patients 2.
• Considering small bowel biopsy for definitive diagnosis, especially if serological tests are inconclusive or if there is a high clinical suspicion for celiac disease 5.
• Evaluating the patient's response to a gluten-free diet as part of the diagnostic process 5.

It's essential to note that the utility of isolated tTG IgG in diagnosing celiac disease is low, at about 3%, indicating that relying solely on this marker may not be sufficient for diagnosis 6.