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Diagnostic Guidelines for Celiac Disease: Managing the Selective IgA Deficiency Challenge
Celiac disease (CD) diagnosis has advanced significantly over the past decade. Global guidelines now emphasize a combination of serology, genetics, and histology. While regional approaches differ, all aim for accurate diagnosis with minimal invasiveness. Core serological markers include antibodies against tissue transglutaminase (tTG), deamidated gliadin peptide (DG), and endomysial antibodies (EmA), assessed in both IgA and IgG classes. Selective IgA deficiency (sIgAD) is a critical diagnostic concern, affecting 2–3% of celiac patients—representing an increase of 10- to 15-fold over the general population1. Undiagnosed sIgAD can result in false-negative IgA-based tests, complicating or delaying diagnosis.
Diagnostic Strategies Across the Globe
Celiac diagnostic guidelines differ in their specifics, but most rely on a core combination of serology, biopsy, and, in some cases, HLA typing. In Europe, the updated 2020 updated guidelines of the European Society Paediatric Gastroenterology (ESPGHAN), stress checking total serum IgA early, alongside anti-tTG IgA for initial screening. Anti-DG, EmA IgA and HLA typing for DQ2/DQ8 should be performed as a second step. In cases of confirmed IgA deficiency, IgG-based assays (tTG, DG and EmA) are recommended. In countries where local guidelines were released, like the US2, Italy3 or Germany4, they align with this pediatric approach and provide clearer directions for adult diagnosis.
The World Gastroenterology Organization Global Guidelines offer adaptable strategies depending on available healthcare resources. They emphasize routine measurement of total serum IgA and promote celiac awareness in non-Caucasian populations, where other causes of villous atrophy may be more prevalent5.
Clinical Implications and Missed Diagnoses in the Selective IgA Deficiency
Failure to recognize selective IgA deficiency can delay the start of gluten-free diet and raise long-term risks such as osteoporosis, infertility, even malignancy. Clinicians should remain vigilant when clinical suspicion of celiac disease persists despite negative serologic results. Streamlined, less invasive pathways are the future—measuring serum IgA prevents missed diagnoses and ensures proper treatment.
Celiac Disease Diagnostic Solutions from Medipan & GA Generic Assays
Our portfolio includes multiplex assays for comprehensive serologic testing in celiac disease, such as immunoblots and based IFA kits based on CytoBead® Technology. These platforms simultaneously detect total IgA and antibodies against tissue transglutaminase (tTG), deamidated gliadin peptide (DG), and endomysial antigen (EmA).
By verifying total IgA in parallel, these tests ensure that negative results on specific antigens are not misinterpreted in patients with IgA deficiency—preventing false exclusions and improving diagnostic accuracy.
In addition, we provide ELISA kits for the separate detection of anti-tTG and anti-DG antibodies (IgA and IgG), as well as IFA kits for EmA detection.
Immunoblot (left) and IFA CytoBead® (right) for measuring IgA , anti-DG and anti-tTG. Positive results are shown as dark spots on the immunoblot and green fluorescent beads on the IFA CytoBead®. Results from a person:
A) healthy and IgA-positive;
B) with celiac disease and positive for IgA, anti-tTG, and anti-DG as well as positive for EmA on esophagus section;
C) with selective IgA deficiency and both tests completely negative.
The immunoblot also contains a negative control and the CytoBead® contains a section of the esophagus of a monkey.
Related products with integrated IgA control
| IFA tests (CytoBead® Technology) | |
|---|---|
| 8064 – CytoBead® CeliAK | Determination of anti-tTG, anti-DG, and control of IgA antibodies, as well as EmA (IgA or IgG). |
| 4271 – AKLIDES® CytoBead® CeliAK | Quantitative determination of anti-tTG, anti-DG, and control of IgA antibodies, as well as EmA (IgA or IgG), and use on the automated system akiron® NEO. |
| Immunoblot tests | |
|---|---|
| 4208 – CeliAK IgA LINE | Determination of anti-tTG, anti-DG, and control of IgA antibodies. |
| 5014 – DotDiver CeliAK IgA | Determination of anti-tTG, anti-DG, and control of IgA antibodies, and use on the automated system DotDiver2.0. |
Discover the full range of products related to celiac disease diagnostics:
References
- Kumar, et al. (2002), Celiac Disease and Immunoglobulin A Deficiency: How Effective Are the Serological Methods of Diagnosis? ↩︎
- Rubio-Tapia, et al. (2023), American College of Gastroenterology Guidelines
Update: Diagnosis and Management of Celiac Disease ↩︎ - Zingone, et al. (2022), Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis ↩︎
- Felber, et al. (2021) Aktualisierte S2k-Leitlinie Zöliakie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) ↩︎
- Bai , et al. (2016) World Gastroenterology Organisation Global Guidelines – Celiac Disease ↩︎