What are the typical laboratory findings in the bloodwork of an undiagnosed celiac disease patient?

Typical Laboratory Findings in Undiagnosed Celiac Disease

The most reliable serological marker for undiagnosed celiac disease is elevated IgA tissue transglutaminase (tTG) antibodies, with sensitivity of 90.7% in adults and 97.7% in children, alongside IgA endomysial antibodies (EMA) which have higher specificity at 99.6% in adults and 93.8% in children. 1

Primary Serological Markers

IgA-based Tests

• IgA tissue transglutaminase (tTG):

  • Adult sensitivity: 90.7% (87.3-93.2%)
  • Adult specificity: 87.4% (84.4-90.0%)
  • Child sensitivity: 97.7% (91.0-99.4%)
  • Child specificity: 70.2% (39.3-89.6%) 1

• IgA endomysial antibodies (EMA):

  • Adult sensitivity: 88.0% (75.2-94.7%)
  • Adult specificity: 99.6% (92.3-100%)
  • Child sensitivity: 94.5% (88.9-97.3%)
  • Child specificity: 93.8% (85.2-97.5%) 1

• IgA deamidated gliadin peptide (DGP):

  • Adult sensitivity: 96.4% (91.7-98.5%)
  • Adult specificity: 95.4% (93.6-96.8%) 1

Alternative Tests for IgA Deficiency

• IgG deamidated gliadin peptide (DGP):

  • Adult sensitivity: 93.6% (88.6-96.5%)
  • Adult specificity: 99.4% (98.5-99.7%) 1

• IgG tissue transglutaminase (tTG):

  • Used when IgA deficiency is present 1

Nutritional Deficiencies and Other Laboratory Findings

Undiagnosed celiac disease patients commonly present with:

• Folate deficiency: Significantly more common in undiagnosed patients compared to diagnosed patients on treatment 2
• Iron deficiency anemia: Common finding in undiagnosed patients 2
• Normal total IgA levels: Important to check as IgA deficiency occurs in some celiac patients 1

Testing Algorithm

1. First-line testing:

   • IgA tissue transglutaminase (tTG) antibodies
   • Total serum IgA level (to rule out IgA deficiency) 1

2. If IgA tTG is positive:

   • In adults: Confirm with duodenal biopsy
   • If weakly positive: Add IgA EMA testing 1
   • High levels (>10x upper limit of normal) with positive EMA have nearly 100% positive predictive value 1

3. If IgA deficiency is present:

   • Test for IgG DGP antibodies or IgG tTG antibodies 1
   • Note: IgG tTG is not specific without IgA deficiency 1

Important Caveats

• Pre-test considerations: Patient must be on a gluten-containing diet for accurate testing (at least 3 slices of wheat bread daily for 1-3 months before testing) 1
• False negatives: Can occur if patient has reduced gluten intake prior to testing 1
• Obesity: One-third of screen-detected celiac patients may be obese, contrary to the classic presentation 2
• Asymptomatic presentation: Many undiagnosed patients may not present with typical gastrointestinal symptoms 2
• Discordant results: About 8% of celiac patients may be EMA-negative but tTG-positive, highlighting the importance of using multiple serological tests 3

Special Populations

• IgA-deficient patients: Approximately 2-3% of celiac patients have IgA deficiency, requiring IgG-based testing 1
• High-risk groups: First-degree relatives of celiac patients and those with type 1 diabetes, autoimmune thyroid disease, or Down syndrome should be considered for screening even with atypical symptoms 4

Early detection and treatment of celiac disease is critical to prevent long-term complications such as osteoporosis, infertility, and increased risk of small bowel cancer, which can significantly impact morbidity and mortality 4.