What is the interpretation and management of celiac disease in an individual with Human Leukocyte Antigen (HLA) DQ2 present and HLA DQ8 absent?

Interpretation of HLA DQ2/DQ8 Testing in Celiac Disease: DQ2 Present, DQ8 Absent

The presence of HLA DQ2 indicates genetic susceptibility to celiac disease, but alone is insufficient for diagnosis and requires additional testing such as serology and possibly duodenal biopsy to confirm or exclude celiac disease.

Significance of HLA DQ2 Positivity

HLA DQ2 positivity indicates that the individual has the genetic predisposition to develop celiac disease. However, this finding must be interpreted with important caveats:

• HLA DQ2 is present in 25-40% of the general population, while only 2-3% of these genetically susceptible individuals will develop celiac disease 1
• HLA testing has a high negative predictive value (>99%) but very low positive predictive value 1
• The presence of HLA DQ2 alone cannot confirm celiac disease diagnosis 1

Diagnostic Algorithm for Individuals with HLA DQ2 Present

Step 1: Serological Testing

• First-line test: IgA tissue transglutaminase antibodies (TG2-IgA) 1
• Additional testing if indicated:
  • IgA endomysial antibodies (EMA) as a confirmatory test due to high specificity 1
  • Total IgA levels to rule out IgA deficiency 1
  • If IgA deficient, use IgG-based tests (IgG-TG2 or IgG-DGP) 1

Step 2: Duodenal Biopsy (if serology positive or high clinical suspicion)

• Multiple biopsies recommended (at least 4 from distal duodenum and 1-2 from bulb) 1
• Histological findings supporting celiac disease:
  • Villous atrophy
  • Increased intraepithelial lymphocytes
  • Crypt hyperplasia

Step 3: Clinical Correlation

• Assess response to gluten-free diet if diagnosis is established
• Monitor with follow-up serology at 6 and 12 months, then yearly 1

Important Clinical Considerations

1. Avoid gluten restriction before testing:

   • Patients must not reduce or eliminate gluten before diagnostic testing as this reduces accuracy of both serological and histological results 1
   • If patient has already started a gluten-free diet, recommend consuming 1-3 slices of gluten-containing bread daily for 1-3 months before testing 1

2. Risk stratification based on HLA status:

   • First-degree relatives with HLA DQ2 have approximately 16-fold increased risk of developing celiac disease 1
   • Regular serological screening may be warranted in high-risk individuals 1

3. Potential for seronegative celiac disease:

   • In cases with strong clinical suspicion despite negative serology, duodenal biopsy should still be pursued 1
   • HLA typing is particularly useful in patients with equivocal small-bowel histologic findings 1

Pitfalls to Avoid

1. Overinterpretation of HLA results:

   • Remember that HLA DQ2 positivity alone is insufficient for diagnosis due to its high prevalence in the general population 1
   • HLA testing should be used primarily to rule out celiac disease when negative 1

2. Incomplete HLA testing interpretation:

   • Ensure complete allele testing is reported (DQA10501, DQB10201 for DQ2.5; DQA10201, DQB10202 for DQ2.2) 1
   • Rarely, patients with only half of the DQ2.5 heterodimer may still develop celiac disease 2

3. Ignoring other causes of enteropathy:

   • If serology is negative but symptoms persist, consider other causes of villous atrophy or enteropathy 1

In summary, HLA DQ2 positivity indicates genetic susceptibility to celiac disease but requires correlation with serological testing, histological findings, and clinical presentation for definitive diagnosis. The absence of HLA DQ8 does not affect this interpretation, as either DQ2 or DQ8 is sufficient for genetic susceptibility.