HLA Genotyping and Celiac Disease Risk in Children
Even with positive HLA-DQ2 or DQ8 genotyping, a child can still develop celiac disease at any age, as these genetic markers only indicate susceptibility but do not guarantee or prevent disease development. 1
Understanding HLA Genotyping in Celiac Disease
HLA genotyping provides important information about celiac disease risk but has limitations:
- HLA-DQ2 and DQ8 are present in >99% of people with celiac disease, making their absence highly valuable for ruling out the disease 1
- However, these genetic markers are found in approximately 30% of the general population, so a positive result only indicates susceptibility 1, 2
- The positive predictive value of HLA genotyping is very low, as only 2-3% of genetically susceptible individuals will develop celiac disease during their lifetime 1
Risk Assessment Based on HLA Status
The risk of developing celiac disease varies significantly based on specific HLA genotypes:
- Highest risk: Children homozygous for DQ2.5 haplotype (up to 29% risk) 3, 4
- Moderate risk: Heterozygous carriers of DQ2.5 with DQB1*02 allele 3
- Lower risk: Carriers of a single copy of DQB102 or DQA105 allele 3
- Negligible risk (<1%): Children negative for both DQ2 and DQ8 4, 5
Monitoring Recommendations for At-Risk Children
For children with positive HLA-DQ2 or DQ8 genotyping:
- Regular serological screening with tissue transglutaminase IgA (tTG-IgA) is recommended 1, 2
- Monitoring should continue throughout childhood and adolescence as celiac disease can develop at any age 1
- First-degree relatives of celiac patients have a 7.5% overall risk of developing the disease 1, 4
- High-risk HLA genotypes significantly increase this risk (up to 38% by age 10 for high-risk genotypes) 6
Important Considerations
- HLA genotyping's primary value is its negative predictive value—ruling out celiac disease when negative 1, 5
- A positive HLA test alone is insufficient for diagnosis and requires clinical correlation and serological testing 1
- Total serum IgA should be checked with tTG-IgA to rule out IgA deficiency, which is 10-15 times more common in celiac patients 1, 2
- For IgA-deficient patients, IgG-based testing (IgG-DGP, IgG-tTG) should be performed 1, 2
When to Consider Endoscopy
- Positive celiac serology (tTG-IgA) warrants upper endoscopy with multiple duodenal biopsies 1, 2
- At least 6 biopsy specimens should be taken from both the duodenal bulb and distal duodenum 2
- Even with negative serology, duodenal biopsy should be considered if clinical suspicion is high 1
In summary, while HLA genotyping provides valuable information about celiac disease risk, a positive result only indicates susceptibility, and children with these genetic markers can develop celiac disease at any point in their lives. Regular monitoring with serological testing is essential for early detection and management.