Is a serum immunoglobulin E (IgE) antibody test relevant for celiac disease, eosinophilic esophagitis, ankylosing spondylitis, or Crohn disease?

Serum IgE Testing Is Not Relevant for Celiac Disease, Ankylosing Spondylitis, or Crohn's Disease, but May Have Limited Utility in Eosinophilic Esophagitis

Serum IgE antibody testing plays no role in the diagnosis or management of celiac disease, ankylosing spondylitis, or Crohn's disease, but may be considered in eosinophilic esophagitis when IgE-mediated food allergy is suspected as a contributing factor.

Celiac Disease

Celiac disease diagnosis relies exclusively on IgA-based serologic markers and duodenal biopsy—IgE testing has no diagnostic value.

• IgA tissue transglutaminase (tTG-IgA) is the preferred first-line screening test, with sensitivity of 90.7% and specificity of 87.4% in adults at 15 U/mL threshold 1.
• IgA endomysial antibody (EMA) serves as a confirmatory test with excellent specificity of 99.6% in adults 1.
• Total IgA measurement must accompany tTG-IgA testing to detect IgA deficiency, which occurs in 1-3% of celiac patients and causes falsely negative IgA-based results 1, 2.
• In IgA-deficient patients, IgG deamidated gliadin peptide (DGP-IgG) is the preferred alternative, with 93.6% sensitivity and 99.4% specificity 1, 2, 3.

IgE antibodies are not part of the celiac disease diagnostic pathway because celiac disease is a T-cell mediated autoimmune enteropathy, not an IgE-mediated allergic condition 1.

Common Pitfall

Do not confuse celiac disease with IgE-mediated wheat allergy—these are distinct entities with different pathophysiology and require different diagnostic approaches 1.

Eosinophilic Esophagitis (EoE)

Serum IgE testing has limited and non-definitive utility in EoE evaluation.

• Skin prick tests (SPTs), serum specific IgE (sIgE), and atopy patch tests (APTs) may be considered to help identify foods associated with EoE, but these tests alone are insufficient to establish causation 1.
• The diagnosis of food-triggered EoE requires resolution of symptoms and esophageal eosinophilia following dietary elimination, and recurrence with food reintroduction—not positive IgE testing 1.
• EoE is primarily a non-IgE-mediated, T-cell driven disorder, though some patients may have concurrent IgE-mediated food allergies 1, 4.

Evidence of Overlap

• A case report documented concurrent celiac disease, EoE, and IgE-mediated food allergy in a single pediatric patient, demonstrating that these conditions can coexist but remain pathophysiologically distinct 4.
• A pediatric cohort study found 7.4% of children with celiac disease also had EoE, with elevated peripheral absolute eosinophil counts (454.1 ± 122.7 vs 231.9 ± 19.4 per μL, P = .003) predicting concurrent EoE 5.
• A large cross-sectional study showed patients with active celiac disease had 26% higher odds of esophageal eosinophilia (adjusted OR 1.26,95% CI 0.98-1.60) compared to those without celiac disease 6.

Clinical Application

When evaluating a patient with suspected EoE, serum IgE testing may identify concurrent IgE-mediated food allergies that require separate management, but positive IgE results do not confirm EoE diagnosis 1. The gold standard for EoE diagnosis remains esophageal biopsy showing ≥15 eosinophils per high-power field after excluding other causes 1.

Ankylosing Spondylitis

IgE testing has no established role in ankylosing spondylitis diagnosis or management.

• A case-controlled study found 36.7% of ankylosing spondylitis patients were positive for anti-gliadin antibodies (AGA), but this represents a non-IgE immune response potentially related to intestinal permeability 7.
• Only one of these AGA-positive patients had histologically confirmed celiac disease, and IgE antibodies were not measured or implicated in the pathogenesis 7.

Serum IgE testing provides no diagnostic or prognostic information for ankylosing spondylitis, which is an HLA-B27-associated seronegative spondyloarthropathy 7.

Crohn's Disease

IgE antibody testing is not part of the Crohn's disease diagnostic workup.

• Crohn's disease diagnosis relies on inflammatory markers (fecal calprotectin, fecal lactoferrin), endoscopy, and histopathology—not IgE testing 1.
• The AGA technical review on diarrhea evaluation discusses inflammatory bowel disease screening but does not mention IgE testing as a relevant diagnostic tool 1.

Distinguishing IBD from IBS

When evaluating chronic diarrhea, fecal calprotectin and fecal lactoferrin are the appropriate screening tests to distinguish inflammatory bowel disease (including Crohn's) from irritable bowel syndrome, not serum IgE 1.

Summary Algorithm

For suspected celiac disease:

• Order tTG-IgA + total IgA (never IgE) 1, 2, 3
• If positive, confirm with EMA and proceed to duodenal biopsy 1, 2

For suspected eosinophilic esophagitis:

• Proceed directly to esophageal biopsy for diagnosis 1
• Consider serum IgE/SPT only to identify concurrent IgE-mediated food allergies 1
• Use dietary elimination and food challenge to establish causation 1

For ankylosing spondylitis or Crohn's disease:

• IgE testing is not indicated 1, 7
• Use HLA-B27 for ankylosing spondylitis 7
• Use inflammatory markers and endoscopy for Crohn's disease 1