Clinical utility of celiac disease-associated HLA testing

Negative predictive value (NPV) of celiac disease (CD)-related human leukocyte antigens (HLA) DQ2 and DQ8 approaches 100 % in individual patients. However, studies evaluating its exclusionary utility in patient groups are lacking.

We aim to assess the performance of HLA testing when applied to patient groups with varying characteristics and propose evidence-based recommendations for its clinical use.

Demographic and clinical information was recorded in patients undergoing HLA testing. Using predetermined criteria, patients were classified as CD, non-CD, or indeterminate. Diagnostic yield of HLA testing was defined as the percentage of patients in whom CD could be excluded based on negative HLA test.

Two hundred and fifty-six patients underwent testing for CD-related HLA DQ2 and DQ8. 102 (100 non-CD, 2 CD) patients tested HLA negative for a 98 % NPV and 39 % diagnostic yield. Diagnostic yield was highest (60 %) in patients with intraepithelial lymphocytosis plus normal IgA tissue transglutaminase antibody (IgA-tTG) and lowest in patients with positive IgA-tTG plus villous atrophy (0 %). CD was diagnosed in two HLA-negative patients, who carried half of DQ2.5 trans genotype.

Diagnostic yield of CD-related HLA testing varies widely depending on clinical indication. HLA testing is a practical and valuable test for most patients in whom initial evaluation for CD is inconclusive. A negative HLA result usually obviates the need for further celiac testing including endoscopy and gluten challenge. Rarely, in patients reported as HLA negative, half of HLA DQ2.5 (cis or trans) is sufficient for development of CD.