What are the implications of a negative Human Leukocyte Antigen (HLA) test result for celiac disease in a child?

Implications of a Negative HLA Test for Celiac Disease in a Child

A negative HLA test (absence of HLA-DQ2 and HLA-DQ8) in a child virtually excludes celiac disease with a negative predictive value of nearly 100%, making further testing for celiac disease unnecessary unless clinical suspicion remains extremely high. 1

Understanding HLA Testing in Celiac Disease

HLA testing serves as a valuable genetic screening tool with the following implications:

• Exclusionary Power: The absence of HLA-DQ2 and HLA-DQ8 provides a negative predictive value of close to 100%, effectively ruling out celiac disease 2
• Prevalence in Celiac Disease: Over 99% of celiac disease patients carry either HLA-DQ2 (95%) or HLA-DQ8 (5%) 2, 1
• Low Positive Predictive Value: Only 2-3% of individuals with these genetic markers will develop celiac disease during their lifetime 1

Clinical Significance of a Negative HLA Test

A negative HLA test has important implications for clinical management:

• Avoids Unnecessary Testing: Eliminates the need for repeated serological testing and invasive procedures like endoscopy with biopsy 2
• Reduces Anxiety: Provides reassurance to families concerned about celiac disease development
• Cost-Effective: Prevents expenditure on ongoing screening and monitoring 1

When to Consider HLA Testing

HLA testing is particularly valuable in specific clinical scenarios:

• Unclear Diagnosis: When serological tests and clinical presentation yield conflicting or inconclusive results 2
• Already on Gluten-Free Diet: For patients who started a gluten-free diet before proper testing was completed 1
• Family Screening: For first-degree relatives of celiac patients who have a 7.5% overall risk of developing the disease 1
• High-Risk Groups: Children with type 1 diabetes, Down syndrome, or other autoimmune disorders 1

Limitations and Caveats

Despite its high negative predictive value, there are important considerations:

• Cannot Confirm Diagnosis: A positive HLA test only indicates susceptibility, not disease presence 1
• Genetic Variations: A very small number of celiac patients may have only partial HLA risk alleles (either DQA105 or DQB102) 2
• Geographic Variations: The prevalence of HLA-DQ2/DQ8 negativity among celiac patients varies by population (up to 24% in some studies) 3

Serological Testing Comparison

When HLA testing is positive or not performed, serological tests remain the primary screening tool:

Test	Sensitivity	Specificity
tTG-IgA	97.7% (children)	70.2% (children)
EMA-IgA	94.5% (children)	93.8% (children)

1, 2

Follow-Up Recommendations After a Negative HLA Test

For a child with a negative HLA test:

• No Routine Celiac Screening: Further celiac-specific testing is generally unnecessary 2
• Alternative Diagnosis: Focus on investigating other causes for gastrointestinal symptoms or growth concerns 4
• Monitoring: If symptoms persist or worsen, consider other gastrointestinal disorders such as inflammatory bowel disease, microscopic colitis, or functional disorders 2

Clinical Perspective

Research shows that children with positive celiac serology often have subtle clinical manifestations:

• Mild alterations in growth and nutrition
• More frequent reports of irritability/lethargy
• Abdominal distention/gas
• Difficulty with weight gain 5

These symptoms should prompt consideration of alternative diagnoses in HLA-negative children.