What is the significance of low Immunoglobulin A (IgA), in a normal celiac disease panel?

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From the Guidelines

Low Immunoglobulin A (IgA) levels in a normal celiac disease panel are significant because they may indicate selective IgA deficiency, which can lead to false negative results in serological tests for celiac disease.

Key Points to Consider

  • Selective IgA deficiency is more common in patients with celiac disease, occurring in approximately 2.6% of cases 1.
  • In patients with suspected celiac disease and low IgA levels, IgG-based tests, such as IgG anti-tissue transglutaminase (tTG) or IgG deamidated gliadin peptide (DGP), should be considered 1.
  • Measuring total IgA levels is an important step in the diagnosis of celiac disease, particularly in patients with negative serologic test results and a high suspicion of celiac disease 1.
  • A diagnosis of celiac disease with selective IgA deficiency can be made if the patient has a low total IgA level and positive IgG-based tests 1.

Clinical Implications

  • Clinicians should be aware of the potential for selective IgA deficiency in patients with celiac disease and take this into consideration when interpreting serological test results.
  • Patients with low IgA levels and suspected celiac disease should undergo further evaluation, including IgG-based tests and potentially intestinal biopsy, to confirm the diagnosis 1.

From the Research

Significance of Low Immunoglobulin A (IgA) in Celiac Disease Panel

  • Low IgA levels can lead to false-negative results in serological tests for celiac disease, such as IgA-endomysial antibody (EMA) and IgA-tissue transglutaminase (TG) tests 2, 3, 4
  • IgA deficiency is more common in patients with celiac disease, with a prevalence of 2-3% in celiac patients 3, 5
  • Patients with selective IgA deficiency have a 10- to 20-fold increased risk of celiac disease 6
  • In patients with IgA deficiency, alternative tests such as IgG-based assays (e.g., IgG-EMA, IgG-TG) may be used to diagnose celiac disease, but their reliability is limited 2, 6, 4
  • Intestinal biopsy is often necessary to confirm the diagnosis of celiac disease in patients with IgA deficiency 2, 3, 4

Clinical Implications

  • IgA deficiency can lead to underdiagnosis of celiac disease, as serological tests may be negative or inconclusive 2, 3, 4
  • Patients with IgA deficiency and suspected celiac disease should undergo intestinal biopsy to confirm the diagnosis 2, 3, 4
  • Clinicians should be aware of the potential for IgA deficiency in patients with celiac disease and use alternative diagnostic approaches when necessary 2, 3, 6, 4

Association with Autoimmune Diseases

  • IgA deficiency is associated with an increased risk of autoimmune diseases, including celiac disease 5
  • Patients with IgA deficiency and celiac disease may have a lower incidence of autoimmune diseases compared to those without IgA deficiency 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Prevalence and characteristics of selective IgA deficiency in celiac patients].

Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru, 2021

Research

The clinical significance of immunoglobulin A deficiency.

Annals of clinical biochemistry, 2007

Research

Selective immunoglobulin A deficiency and celiac disease: let's give serology a chance.

Journal of investigational allergology & clinical immunology, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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