If I had a negative Human Leukocyte Antigen (HLA) test as a child, is it likely I won't develop celiac disease as an adult?

HLA Testing and Celiac Disease Risk Assessment

A negative HLA-DQ2 and HLA-DQ8 test as a child provides a near 100% negative predictive value, effectively ruling out the possibility of developing celiac disease as an adult. 1

Understanding HLA Testing in Celiac Disease

HLA testing serves as a powerful genetic screening tool for celiac disease risk assessment:

• Over 99% of celiac disease patients carry either HLA-DQ2 (95%) or HLA-DQ8 (5%) genetic markers 1
• The absence of these markers provides a negative predictive value approaching 100%, essentially eliminating the possibility of developing celiac disease 1
• A very small number of celiac patients may have only partial HLA risk alleles (either DQA105 or DQB102), but complete absence of all risk alleles makes celiac disease extremely unlikely 1

Clinical Implications of Negative HLA Testing

For individuals with negative HLA testing in childhood:

• Further celiac-specific testing is generally unnecessary throughout life 1
• The risk of developing celiac disease approaches zero, as demonstrated in multiple studies 2, 3
• In a study of family members of celiac patients, those lacking susceptible HLA factors were not affected by celiac disease, despite having a higher baseline risk due to family history 3

Risk Stratification Based on HLA Status

HLA status creates a clear risk gradient for celiac disease development:

• Individuals with both DQ2 and DQ8 have the highest risk (approximately 1:7) 3
• Those completely lacking all predisposing HLA factors have an extremely low risk (approximately 1:2518) 3
• In a study of pediatric celiac patients, no patients were negative for all the alleles predisposing to celiac disease 2

Important Caveats and Considerations

While a negative HLA test is highly reassuring, there are important considerations:

• If gastrointestinal symptoms persist despite negative HLA testing, other conditions should be investigated, such as:

  • Inflammatory bowel disease
  • Microscopic colitis
  • Functional gastrointestinal disorders 1

• The quality of HLA testing is important - ensure testing included comprehensive analysis for:

  • HLA-DQ2 (DQA105 and DQB102)
  • HLA-DQ8 (DQA103 and DQB103:02)
  • Partial risk alleles (DQA105 or DQB102 alone) 1, 2

Conclusion for Clinical Practice

For individuals with confirmed negative HLA-DQ2 and HLA-DQ8 testing in childhood:

• No routine celiac disease screening is required in adulthood
• The lifetime risk of developing celiac disease is extremely low, approaching zero
• Focus diagnostic efforts on other causes if gastrointestinal symptoms develop

This approach aligns with guidelines that recognize HLA testing's value in ruling out celiac disease with near certainty, eliminating the need for repeated serological testing and invasive procedures like endoscopy with biopsy 1.