HLA Typing May Uncover Patients Incorrectly Labelled With Coeliac Disease: CGH | August 2026 | Population-Based HUNT4 Study
Introduction:
HLA-DQ2/DQ8 testing is highly sensitive but poorly specific for coeliac disease. The HUNT4 study examined whether HLA typing can help identify patients carrying a historical coeliac diagnosis that may be incorrect.
Why was this study needed?
Some patients remain labelled with coeliac disease despite incomplete original diagnostic documentation.
Reassessment is difficult once a patient has adopted a gluten-free diet.
HLA testing may be particularly useful for excluding coeliac disease.
Key Findings:
52,588 Norwegian adults underwent population-based screening.
Every newly biopsy-confirmed coeliac patient carried HLA-DQ2.5, DQ2.2, or DQ8.
Among 376 participants with a previous coeliac diagnosis, 21 lacked these susceptibility HLA types.
On histological reassessment, only 5 of these 21 had evidence supporting coeliac disease.
Absence of relevant HLA types provided approximately 99–100% negative predictive value after reassessment.
HLA testing may therefore be particularly valuable when reviewing a legacy, uncertain, or poorly documented diagnosis.
Conversely, HLA-DQ2/DQ8 positivity is common and has low positive predictive value.
Bottom Line:
HLA testing is most useful for ruling out—not confirming—coeliac disease. A negative susceptibility genotype should prompt careful reassessment of an uncertain historical diagnosis.
